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Xu YW, Peng YH, Liu CT, Chen H, Chu LY, Chen HL, Wu ZY, Wei WQ, Xu LY, Wu FC, Li EM. Machine learning technique-based four-autoantibody test for early detection of esophageal squamous cell carcinoma: a multicenter, retrospective study with a nested case-control study. BMC Med 2025; 23:235. [PMID: 40264204 PMCID: PMC12016149 DOI: 10.1186/s12916-025-04066-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 04/10/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Autoantibodies represent promising diagnostic blood-based biomarkers that may be generated prior to the first clinically detectable signs of cancers. In present study, we aimed to identify a novel optimized autoantibody panel with high diagnostic accuracy for clinical and preclinical esophageal squamous cell carcinoma (ESCC) using machine learning (ML) algorithms. METHODS We identified potential autoantibodies against tumor-associated antigens with serological proteome analysis. Serum autoantibody levels were measured by ELISA. Using a training set (n = 531), 102 models based on ML algorithms were constructed, and Partial Least Squares Generalized Linear Models (plsRglm) was selected out using receiver operating characteristics (ROC), Kolmogorov-Smirnov (K-S) test, and Population Stability Index (PSI), and further validated through an internal validation set (n = 413), external validation set 1 (n = 371), and external validation set 2 (n = 202). Then, we validated the ability of plsRglm model in predicting preclinical ESCC by a nested case-control study (24 preclinical ESCCs and 112 matched controls) within a population-based prospective cohort study. RESULTS ROC analysis, K-S test, and PSI showed that plsRglm model based on four autoantibodies (ALDOA, ENO1, p53, and NY-ESO-1) exhibited the better diagnostic performance and robustness, which provided a high diagnostic accuracy in diagnosing ESCC with the respective AUCs (sensitivities and specificities) of 0.860 (68.8% and 90.4%) in the training set, 0.826 (65.3% and 89.1%) in the internal validation set, and 0.851 (69.2% and 87.3%) in the external validation set 1. For early-stage ESCC, this signature also maintained diagnostic performance [0.817 (62.3% and 90.4%) in the training set; 0.842 (62.5% and 89.1%) in the internal validation set; 0.854 (63.2% and 87.3%) in the external validation set 1; and 0.850 (67.3% and 90.1%) in the external validation set 2]. In the nested case-control study, this plsRglm model could detect the presence of preclinical ESCC with the AUC of 0.723, sensitivity of 54.2%, and specificity of 86.6%. CONCLUSIONS Our findings indicated that the plsRglm model based on four autoantibodies might help identify preclinical and early-stage ESCC.
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Affiliation(s)
- Yi-Wei Xu
- Department of Clinical Laboratory Medicine, Esophageal Cancer Prevention and Control Research Center, Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China.
- Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China.
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, Esophageal Cancer Prevention and Control Research Center, Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China
- Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, Esophageal Cancer Prevention and Control Research Center, Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China
- Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China
| | - Hao Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Ling-Yu Chu
- Department of Clinical Laboratory Medicine, Esophageal Cancer Prevention and Control Research Center, Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Hai-Lu Chen
- Department of Surgical Oncology, Shantou Central Hospital, Shantou, 515031, China
| | - Zhi-Yong Wu
- Department of Surgical Oncology, Shantou Central Hospital, Shantou, 515031, China
| | - Wen-Qiang Wei
- Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Li-Yan Xu
- Institute of Oncological Pathology, Shantou University Medical College, Shantou, 515041, China.
| | - Fang-Cai Wu
- Department of Radiation Oncology, Esophageal Cancer Prevention and Control Research Center, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China.
| | - En-Min Li
- Esophageal Cancer Prevention and Control Research Center, Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China.
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, China.
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Chu LY, Wu FC, Fang WK, Hong CQ, Huang LS, Zou HY, Peng YH, Chen H, Xie JJ, Xu YW. Secreted proteins encoded by super enhancer-driven genes could be promising biomarkers for early detection of esophageal squamous cell carcinoma. Biomed J 2024; 47:100662. [PMID: 37774793 PMCID: PMC11340493 DOI: 10.1016/j.bj.2023.100662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 08/25/2023] [Accepted: 09/22/2023] [Indexed: 10/01/2023] Open
Abstract
BACKGROUND Early detection of cancer remains an unmet need in clinical practice, and high diagnostic sensitivity and specificity biomarkers are urgently required. Here, we attempted to identify secreted proteins encoded by super-enhancer (SE)-driven genes as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). METHODS We conducted an integrative analysis of multiple data sets including ChIP-seq data, secretome data, CCLE data and GEO data to screen secreted proteins encoded by SE-driven genes. Using ELISA, we further identified up-regulated secreted proteins through a small size of clinical samples and verified in a multi-centre validation stage (345 in test cohort and 231 in validation cohort). Receiver operating characteristic curves were used to calculate diagnostic accuracy. Artificial intelligence (AI) method named gradient boosting machine (GBM) were applied for model construction to enhance diagnostic accuracy. RESULTS Serum EFNA1 and MMP13 were identified, and showed significantly higher levels in ESCC patients compared to normal controls. An integrated Five-Biomarker Panel (iFBPanel) established by combining EFNA1, MMP13, carcino-embryonic antigen, Cyfra21-1 and squmaous cell carcinoma antigen had AUCs of 0.881 and 0.880 for ESCC in test and validation cohorts, respectively. Importantly, the iFBPanel also exhibited good performance in detecting early-stage ESCC patients (0.872 and 0.864). Furthermore, the iFBPanel was further empowered by AI technology which showed excellent diagnostic performance in early-stage ESCC (0.927 and 0.907). CONCLUSIONS Our study suggested that serum EFNA1 and MMP13 could potentially assist ESCC detection, and provided an easy-to-use detection model that might help the diagnosis of early-stage ESCC.
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Affiliation(s)
- Ling-Yu Chu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Fang-Cai Wu
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shanto, China; Guangdong Esophageal Cancer Institute, Cancer Hospital of Shantou University Medical College, Shanto, China; Esophageal Cancer Prevention and Control Research Centre, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Wang-Kai Fang
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Chao-Qun Hong
- Department of Oncological Laboratory Research, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Li-Sheng Huang
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shanto, China
| | - Hai-Ying Zou
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China; Guangdong Esophageal Cancer Institute, Cancer Hospital of Shantou University Medical College, Shanto, China
| | - Hao Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Centre, Guangzhou, China.
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China; Guangdong Esophageal Cancer Institute, Cancer Hospital of Shantou University Medical College, Shanto, China; Esophageal Cancer Prevention and Control Research Centre, Cancer Hospital of Shantou University Medical College, Shantou, China.
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Zheng YQ, Huang HH, Chen SX, Xu XE, Li ZM, Li YH, Chen SZ, Luo WX, Guo Y, Liu W, Li EM, Xu LY. Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma. J Proteomics 2024; 304:105233. [PMID: 38925350 DOI: 10.1016/j.jprot.2024.105233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 06/19/2024] [Accepted: 06/22/2024] [Indexed: 06/28/2024]
Abstract
Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.
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Affiliation(s)
- Ya-Qi Zheng
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510000, China
| | - Hai-Hua Huang
- Department of Pathology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Shu-Xian Chen
- Department of Digestive Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Xiu-E Xu
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Zhi-Mao Li
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Yue-Hong Li
- Department of Digestive Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Su-Zuan Chen
- Department of Digestive Endoscopy, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Wen-Xiong Luo
- Department of Endoscopy, Shantou Central Hospital, Shantou, Guangdong 515041, China
| | - Yi Guo
- Department of Endoscopy, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Wei Liu
- College of Science, Heilongjiang Institute of Technology, Harbin, Heilongjiang 150000, China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China.
| | - Li-Yan Xu
- Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China.
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4
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Zhao YX, Zhao HP, Zhao MY, Yu Y, Qi X, Wang JH, Lv J. Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:2638-2656. [PMID: 38855150 PMCID: PMC11154680 DOI: 10.3748/wjg.v30.i20.2638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/26/2024] [Accepted: 05/13/2024] [Indexed: 05/27/2024] Open
Abstract
As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.
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Affiliation(s)
- Yi-Xin Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Meng-Yao Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Xi Qi
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
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5
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Zhao Y, Ma C, Cai R, Xin L, Li Y, Ke L, Ye W, Ouyang T, Liang J, Wu R, Lin Y. NMR and MS reveal characteristic metabolome atlas and optimize esophageal squamous cell carcinoma early detection. Nat Commun 2024; 15:2463. [PMID: 38504100 PMCID: PMC10951220 DOI: 10.1038/s41467-024-46837-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 03/06/2024] [Indexed: 03/21/2024] Open
Abstract
Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning and WGCNA. Aberrations in 'alanine, aspartate and glutamate metabolism' proved to be prevalent throughout the ESCC evolution, consistently identified by NMR and MS, and reflected in 16 serum and 10 urine metabolic signatures in both discovery and validation sets. NMR-based simplified panels of any five serum or urine metabolites outperform clinical serological tumor markers (AUC = 0.984 and 0.930, respectively), and are effective in distinguishing early-stage ESCC in test set (serum accuracy = 0.994, urine accuracy = 0.879). Collectively, NMR-based biofluid screening can reveal characteristic metabolic events of ESCC and be feasible for early detection (ChiCTR2300073613).
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Affiliation(s)
- Yan Zhao
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Central Laboratory, Clinical Research Center, Shantou Central Hospital, Shantou, Guangdong, China
| | - Changchun Ma
- Radiation Oncology Department, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Rongzhi Cai
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Lijing Xin
- Animal Imaging and Technology Core, Center for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Yongsheng Li
- Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Lixin Ke
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Wei Ye
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Ting Ouyang
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Jiahao Liang
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Renhua Wu
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
| | - Yan Lin
- Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
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Rao D, Lu H, Wang X, Lai Z, Zhang J, Tang Z. Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer. eLife 2023; 12:e86209. [PMID: 37966470 PMCID: PMC10651172 DOI: 10.7554/elife.86209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 10/17/2023] [Indexed: 11/16/2023] Open
Abstract
Esophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes from eight pairs of EC patients using label-free quantification proteomics profiling and have analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate the candidate proteins from plasma-derived exosomes in 122 EC patients. Of the 803 differentially expressed proteins discovered in cancer and paracancer tissue-derived exosomes, 686 were up-regulated and 117 were down-regulated. Intercellular adhesion molecule-1 (CD54) was identified as an up-regulated candidate for further investigation, and its high expression in cancer tissues of EC patients was validated using immunohistochemistry, real-time quantitative PCR (RT-qPCR), and western blot analyses. In addition, plasma-derived exosome NanoFCM data from 122 EC patients concurred with our proteomic analysis. The receiver operating characteristic (ROC) analysis demonstrated that the AUC, sensitivity, and specificity values for CD54 were 0.702, 66.13%, and 71.31%, respectively, for EC diagnosis. Small interference (si)RNA was employed to silence the CD54 gene in EC cells. A series of assays, including cell counting kit-8, adhesion, wound healing, and Matrigel invasion, were performed to investigate EC viability, adhesive, migratory, and invasive abilities, respectively. The results showed that CD54 promoted EC proliferation, migration, and invasion. Collectively, tissue-derived exosomal proteomics strongly demonstrates that CD54 is a promising biomarker for EC diagnosis and a key molecule for EC development.
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Affiliation(s)
- Dingyu Rao
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical UniversityGanzhouChina
| | - Hua Lu
- The First Clinical School of Medicine of Southern Medical UniversityGuangzhouChina
| | - Xiongwei Wang
- Department of Anesthesiology, Longhua District Central HospitalShenzhenChina
| | - Zhonghong Lai
- Department of Traumatology, First Affiliated Hospital of Gannan Medical UniversityGanzhouChina
| | - Jiali Zhang
- The First School of Clinical Medicine, Gannan Medical UniversityGanzhouChina
| | - Zhixian Tang
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical UniversityGanzhouChina
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7
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Qu H, Tan L, Wu FC, Huang W, Li K, Chen X, Xu YW, Hu X. NY-ESO-1 antigen-antibody interaction process based on an TFBG plasmonic sensor. BIOMEDICAL OPTICS EXPRESS 2023; 14:5921-5931. [PMID: 38021116 PMCID: PMC10659779 DOI: 10.1364/boe.504401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/29/2023] [Accepted: 10/06/2023] [Indexed: 12/01/2023]
Abstract
Autoantibodies against New York esophageal squamous cell cancer 1 (NY-ESO-1) play a crucial role in the diagnosis of esophageal cancer. In this work, a surface plasmonic tilted fiber Bragg grating (TFBG) biosensor is proposed for the detection of NY-ESO-1 antibody, as well as the investigation of the hook effect (which refers to the false negative result in some immunoassays when the concentration of antibodies in the sample is very high) during biomolecular binding between NY-ESO-1 antigen and antibody. The biosensor is made by an 18° TFBG coated with a 50-nm-thick gold film over the fiber surface together with NY-ESO-1 antigens attached to the metallic surface serving as bio-receptors. This biosensor can provide a limit of detection at a concentration of 2 × 10-7 µg/ml with a good linearity in the range from 2 × 10-7 to 2 × 10-5 µg/ml. For a concentration higher than 2 × 10-3 µg/ml, the performance of the sensor probe is reduced owing to the hook effect. Furthermore, experimental results have also demonstrated the repeatability of the proposed biosensor. This proposed biosensor features label-free, compactness, and fast response, which could be potentially applied in the diagnosis of esophageal cancer.
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Affiliation(s)
- Hang Qu
- Research Center for Advanced Optics and Photoelectronics, Department of Physics, College of Science, Shantou University, Shantou, Guangdong 515063, China
| | - Linyao Tan
- Research Center for Advanced Optics and Photoelectronics, Department of Physics, College of Science, Shantou University, Shantou, Guangdong 515063, China
| | - Fang-Cai Wu
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Weiyuan Huang
- Research Center for Advanced Optics and Photoelectronics, Department of Physics, College of Science, Shantou University, Shantou, Guangdong 515063, China
| | - Kaiwei Li
- Key Laboratory of Bionic Engineering of Ministry of Education, Jilin University, Changchun, China
| | - Xiaoyong Chen
- School of Electrical Engineering and Intelligentization, Dongguan University of Technology, Dongguan 523808, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xuehao Hu
- Department of Electromagnetism and Telecommunication, University of Mons, Boulevard Dolez 31, 7000 Mons, Belgium
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Sun G, Ye H, Yang Q, Zhu J, Qiu C, Shi J, Dai L, Wang K, Zhang J, Wang P. Using Proteome Microarray and Gene Expression Omnibus Database to Screen Tumour-Associated Antigens to Construct the Optimal Diagnostic Model of Oesophageal Squamous Cell Carcinoma. Clin Oncol (R Coll Radiol) 2023; 35:e582-e592. [PMID: 37433700 DOI: 10.1016/j.clon.2023.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 05/09/2023] [Accepted: 06/30/2023] [Indexed: 07/13/2023]
Abstract
AIMS Autoantibodies against tumour-associated antigens (TAAs) are promising biomarkers for early immunodiagnosis of cancers. This study was designed to screen and verify autoantibodies against TAAs in sera as diagnostic biomarkers for oesophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS The customised proteome microarray based on cancer driver genes and the Gene Expression Omnibus database were used to identify potential TAAs. The expression levels of the corresponding autoantibodies in serum samples obtained from 243 ESCC patients and 243 healthy controls were investigated by enzyme-linked immunosorbent assay (ELISA). In total, 486 serum samples were randomly divided into the training set and the validation set in the ratio of 2:1. Logistic regression analysis, recursive partition analysis and support vector machine were performed to establish different diagnostic models. RESULTS Five and nine candidate TAAs were screened out by proteome microarray and bioinformatics analysis, respectively. Among these 14 anti-TAAs autoantibodies, the expression level of nine (p53, PTEN, GNA11, SRSF2, CXCL8, MMP1, MSH6, LAMC2 and SLC2A1) anti-TAAs autoantibodies in the cancer patient group was higher than that in the healthy control group based on the results from ELISA. In the three constructed models, a logistic regression model including four anti-TAA autoantibodies (p53, SLC2A1, GNA11 and MMP1) was considered to be the optimal diagnosis model. The sensitivity and specificity of the model in the training set and the validation set were 70.4%, 72.8% and 67.9%, 67.9%, respectively. The area under the receiver operating characteristic curve for detecting early patients in the training set and the validation set were 0.84 and 0.85, respectively. CONCLUSIONS This approach to screen novel TAAs is feasible, and the model including four autoantibodies could pave the way for the diagnosis of ESCC.
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Affiliation(s)
- G Sun
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China
| | - H Ye
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China
| | - Q Yang
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China
| | - J Zhu
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China
| | - C Qiu
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China
| | - J Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
| | - L Dai
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
| | - K Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
| | - J Zhang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
| | - P Wang
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, China.
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9
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Du W, Sun Y, Ji W, Luo T, Zhang D, Guo W, Liang J, Lv Y, Dong M, Li K. Decoding SEC24 Homolog D, COPII coat complex component accuracy as a signature gene in three human cancers. Am J Cancer Res 2023; 13:3686-3704. [PMID: 37693152 PMCID: PMC10492113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 07/01/2023] [Indexed: 09/12/2023] Open
Abstract
Although an increasing body of evidence supports the crucial role of the SEC24 Homolog D, COPII Coat Complex Component (SEC24D) gene in the initiation and progression of cancer, a comprehensive pan-cancer analysis of this gene is still lacking. In this study, we conducted an extensive investigation of SEC24D, aiming to elucidate its potential role and underlying mechanisms across multiple human tumors. Our analysis relied on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To validate our findings, we employed RNA sequencing (RNA-seq), targeted bisulfite sequencing (bisulfite-seq) molecular techniques. Our findings revealed elevated mRNA (Messenger RNA) and protein levels of SEC24D in different tumor tissues. However, the up-regulation of SEC24D was significantly correlated with shorter overall survival (OS), metastasis, and various clinical parameters in esophageal cancer (ESCA), lung adenocarcinoma (LUAD), and kidney renal papillary cell carcinoma (KIRP). Expression validation analysis via RNA-seq and targeted bisulfite-seq analyses, further confirmed the higher expression of SEC24D in LUAD cancer cell lines as compared to normal controls. The DNA methylation level of SEC24D was found to be decreased in ESCA, LUAD, and KIRP samples. DNA methylation analysis via bisulfite-seq analysis also validate the lower promoter methylation level of SE24D in LUAD cell lines relative to controls. Moreover, we observed a significant association between the elevated expression of SEC24D and the levels of infiltrating cells, such as B cells, neutrophils, macrophages, CD8+ T cells, and CD4+ T cells. Analysis of SEC24-related genes revealed that "Protein processing in endoplasmic reticulum, SNARE interaction in vesicular transport, Legionellosis, Pathogenic Escherichia coli infection" were mainly involved in the functional mechanism of SEC24D in ESCA, LUAD, and KIRP. Moreover, we also suggested a few valuable drugs (Acetaminophen, Acteoside, Cyclosporine, Polydatin, Estradiol, Estradiol, Quercetin) for treating ESCA, LUAD, and KIRP patients with respect to overexpressed SEC24D. To summarize, this comprehensive pan-cancer study investigated the association between SEC24D expression and clinical parameters in ESCA, LUAD, KIRP. The study provides valuable insights for further exploring the functional and therapeutic aspects of SEC24D and underscores its predictive significance in the carcinogenesis and prognosis of these specific cancer types.
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Affiliation(s)
- Weiwei Du
- Department of Respiratory and Critical Care Medicine, Zhongshan City People’s HospitalZhongshan, Guangdong, China
- The Zhuhai Campus of The Zunyi Medical UniversityZhuhai, Guangdong, China
| | - Yang Sun
- Baotou Medical CollegeBaotou, Inner Mongolia, China
| | - Wentao Ji
- Department of Respiratory and Critical Care Medicine, Zhongshan City People’s HospitalZhongshan, Guangdong, China
- The Zhuhai Campus of The Zunyi Medical UniversityZhuhai, Guangdong, China
| | - Tian Luo
- Department of Respiratory and Critical Care Medicine, Zhongshan City People’s HospitalZhongshan, Guangdong, China
- Xinxiang Medical UniversityXinxiang, Henan, China
| | - Dandan Zhang
- Department of Respiratory and Critical Care Medicine, Zhongshan City People’s HospitalZhongshan, Guangdong, China
| | - Weihong Guo
- Department of Respiratory and Critical Care Medicine, Zhongshan City People’s HospitalZhongshan, Guangdong, China
| | - Jianping Liang
- Department of Respiratory and Critical Care Medicine, Zhongshan City People’s HospitalZhongshan, Guangdong, China
| | - Yanhua Lv
- Department of Respiratory and Critical Care Medicine, Zhongshan City People’s HospitalZhongshan, Guangdong, China
| | - Mengwei Dong
- Hebei Provincial Hospital of Traditional Chinese MedicineShijiazhuang, Hebei, China
| | - Kaixin Li
- Gansu University of Chinese MedicineLanzhou, Gansu, China
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Liu F, Yuan D, Liu X, Zhuo S, Liu X, Sheng H, Sha M, Ye J, Yu H. A demonstration based on multi-omics transcriptome sequencing data revealed disulfidptosis heterogeneity within the tumor microenvironment of esophageal squamous cell carcinoma. Discov Oncol 2023; 14:96. [PMID: 37306828 DOI: 10.1007/s12672-023-00711-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 06/01/2023] [Indexed: 06/13/2023] Open
Abstract
BACKGROUND It is of great concern to identify prognostic signatures for the prediction and prediction of esophageal squamous cell carcinoma (ESCC), which is the lethal pathological type of malignancy. METHOD Bulk RNA sequencing and scRNA-seq data were retrieved from GSE53624, GSE53622, and GSE188900. Disulfidptosis-related differentially expressed genes (DEGs) were identified between disulfidptosis-high score and disulfidptosis-low score groups. Functional annotation of DEGs were analyzed by Gene Ontology (GO). Consistent clustering and co-expression modules were analyzed, and then constructed a risk score model via multivariate Cox regression analysis. Immune infiltration and immunotherapy response analyses were conducted based on risk score. qRT-PCR, colony formation assay, and flow cytometry analysis were conducted in KYSE-150 and TE-1 cell lines. RESULTS Seven genes (CD96, CXCL13, IL2RG, LY96, TPK1, ACAP1, and SOX17) were selected as marker genes. CD96 and SOX17 are independent prognostic signatures for ESCC patients, with a significant correlation with infiltrated immune cells. ESCC patients had worse response to nivolumab in the high-risk group. Through cellular experiments, we found that CD96 expression was associated with apoptosis and cell cycle ESCC cells. CONCLUSION In a word, the risk score based on disulfidptosis is associated with prognosis and the immune microenvironment, which may direct immunotherapy of ESCC. The key gene of risk score, namely CD96, plays a role in proliferation and apoptosis in ESCC. We offer an insight into the exploration of the genomic etiology of ESCC for its clinical management.
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Affiliation(s)
- Fuxing Liu
- Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
| | - Donglan Yuan
- Department of Gynecology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
| | - Xia Liu
- Department of Pathology, Xuzhou Central Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, 221000, Jiangsu, China
| | - Shichao Zhuo
- Department of Pathology, Xuzhou Central Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, 221000, Jiangsu, China
| | - Xinyun Liu
- Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
| | - Haihui Sheng
- Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
| | - Min Sha
- Translational Medicine Center, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
| | - Jun Ye
- Translational Medicine Center, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
| | - Hong Yu
- Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China.
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Chen Z, Xing J, Zheng C, Zhu Q, He P, Zhou D, Li X, Li Y, Qi S, Ouyang Q, Zhang B, Xie Y, Ren J, Cao B, Zhu S, Huang J. Identification of novel serum autoantibody biomarkers for early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia detection. Front Oncol 2023; 13:1161489. [PMID: 37251926 PMCID: PMC10213680 DOI: 10.3389/fonc.2023.1161489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 04/24/2023] [Indexed: 05/31/2023] Open
Abstract
BACKGROUND Early diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC. METHODS We initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance. RESULTS The serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression. CONCLUSIONS Our data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.
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Affiliation(s)
- Zhibin Chen
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jie Xing
- Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Cuiling Zheng
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qianyu Zhu
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Pingping He
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Donghu Zhou
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaojin Li
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yanmeng Li
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Saiping Qi
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Qin Ouyang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Bei Zhang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yibin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiansong Ren
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bangwei Cao
- Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shengtao Zhu
- Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jian Huang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Qureshi F, Hu W, Loh L, Patel H, DeGuzman M, Becich M, Rubio da Costa F, Gehman V, Zhang F, Foley J, Chitnis T. Analytical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis. Proteomics Clin Appl 2023; 17:e2200018. [PMID: 36843211 DOI: 10.1002/prca.202200018] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 01/24/2023] [Accepted: 02/22/2023] [Indexed: 02/28/2023]
Abstract
PURPOSE To characterize and analytically validate the MSDA Test, a multi-protein, serum-based biomarker assay developed using Olink® PEA methodology. EXPERIMENTAL DESIGN Two lots of the MSDA Test panel were manufactured and subjected to a comprehensive analytical characterization and validation protocol to detect biomarkers present in the serum of patients with multiple sclerosis (MS). Biomarker concentrations were incorporated into a final algorithm used for calculating four Disease Pathway scores (Immunomodulation, Neuroinflammation, Myelin Biology, and Neuroaxonal Integrity) and an overall Disease Activity score. RESULTS Analytical characterization demonstrated that the multi-protein panel satisfied the criteria necessary for a fit-for-purpose validation considering the assay's intended clinical use. This panel met acceptability criteria for 18 biomarkers included in the final algorithm out of 21 biomarkers evaluated. VCAN was omitted based on factors outside of analytical validation; COL4A1 and GH were excluded based on imprecision and diurnal variability, respectively. Performance of the four Disease Pathway and overall Disease Activity scores met the established acceptability criteria. CONCLUSIONS AND CLINICAL RELEVANCE Analytical validation of this multi-protein, serum-based assay is the first step in establishing its potential utility as a quantitative, minimally invasive, and scalable biomarker panel to enhance the standard of care for patients with MS.
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Affiliation(s)
| | - Wayne Hu
- Octave Bioscience, Inc., Menlo Park, California, USA
| | - Louisa Loh
- Octave Bioscience, Inc., Menlo Park, California, USA
| | - Hemali Patel
- Octave Bioscience, Inc., Menlo Park, California, USA
| | | | | | | | - Victor Gehman
- Octave Bioscience, Inc., Menlo Park, California, USA
| | - Fujun Zhang
- Octave Bioscience, Inc., Menlo Park, California, USA
| | - John Foley
- Rocky Mountain Multiple Sclerosis Clinic, Salt Lake City, Utah, USA
| | - Tanuja Chitnis
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Zhang Y, Zhang Y, Peng L, Zhang L. Research Progress on the Predicting Factors and Coping Strategies for Postoperative Recurrence of Esophageal Cancer. Cells 2022; 12:cells12010114. [PMID: 36611908 PMCID: PMC9818463 DOI: 10.3390/cells12010114] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 12/01/2022] [Accepted: 12/20/2022] [Indexed: 12/29/2022] Open
Abstract
Esophageal cancer is one of the malignant tumors with poor prognosis in China. Currently, the treatment of esophageal cancer is still based on surgery, especially in early and mid-stage patients, to achieve the goal of radical cure. However, esophageal cancer is a kind of tumor with a high risk of recurrence and metastasis, and locoregional recurrence and distant metastasis are the leading causes of death after surgery. Although multimodal comprehensive treatment has advanced in recent years, the prediction, prevention and treatment of postoperative recurrence and metastasis of esophageal cancer are still unsatisfactory. How to reduce recurrence and metastasis in patients after surgery remains an urgent problem to be solved. Given the clinical demand for early detection of postoperative recurrence of esophageal cancer, clinical and basic research aiming to meet this demand has been a hot topic, and progress has been observed in recent years. Therefore, this article reviews the research progress on the factors that influence and predict postoperative recurrence of esophageal cancer, hoping to provide new research directions and treatment strategies for clinical practice.
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Affiliation(s)
- Yujie Zhang
- Department of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China
| | - Yuxin Zhang
- Department of Pediatric Surgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China
| | - Lin Peng
- Department of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China
| | - Li Zhang
- Department of Oncology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China
- Correspondence:
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Sun Y, Liu C, Zhong H, Wang C, Xu H, Chen W. Screening of autoantibodies as biomarkers in the serum of renal cancer patients based on human proteome microarray. Acta Biochim Biophys Sin (Shanghai) 2022; 54:1909-1916. [PMID: 36789694 PMCID: PMC10157637 DOI: 10.3724/abbs.2022189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 06/10/2022] [Indexed: 12/13/2022] Open
Abstract
The autoantibody in patients' serum can act as a biomarker for diagnosing cancer, and the differences in autoantibodies are significantly correlated with the changes in their target proteins. In this study, 16 renal cancer (RC) patients were assigned to the disease group, and 16 healthy people were assigned to the healthy control (HC) group. The human proteome microarray consisting of>19,500 proteins was used to examine the differences in IgG and IgM autoantibodies in sera between RC and HC. The comparative analysis of the microarray results shows that 101 types of IgG and 25 types of IgM autoantibodies are significantly higher in RC than in HC. Highly responsive autoantibodies can be candidate biomarkers (e.g., anti-KCNAB2 IgG and anti-RCN1 IgM). Extensive enzyme-linked immunosorbent assay (ELISA) was performed to screen sera in 72 RC patients and 66 healthy volunteers to verify the effectiveness of the new autoantibodies. The AUCs of anti-KCNAB2 IgG and anti-GAPDH IgG were 0.833 and 0.753, respectively. KCNAB2 achieves high protein expression, and its high mRNA level is confirmed to be an unfavorable prognostic marker in clear cell renal cell carcinoma (ccRCC) tissues. This study suggests that the high-throughput human proteome microarray can effectively screen autoantibodies in serum as candidate biomarkers, and their corresponding target proteins can lay a basis for the in-depth investigation into renal cancer.
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Affiliation(s)
- Yangyang Sun
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Department of Urology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen 518039, China
| | - Chengxi Liu
- State Key Laboratory of Chemical Biology and Drug Discovery, Food Safety and Technology Research Centre and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong 999077, China
| | - Huidong Zhong
- Department of Medicinal ChemistryShantou University Medical CollegeShantou515041China
| | - Chenguang Wang
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Haibo Xu
- Department of Urology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen 518039, China
| | - Wei Chen
- Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Department of Urology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen 518039, China
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Tseng YJ, Wang YC, Hsueh PC, Wu CC. Development and validation of machine learning-based risk prediction models of oral squamous cell carcinoma using salivary autoantibody biomarkers. BMC Oral Health 2022; 22:534. [PMID: 36424594 PMCID: PMC9685866 DOI: 10.1186/s12903-022-02607-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 11/18/2022] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION The incidence of oral cavity squamous cell carcinoma (OSCC) continues to rise. OSCC is associated with a low average survival rate, and most patients have a poor disease prognosis because of delayed diagnosis. We used machine learning techniques to predict high-risk cases of OSCC by using salivary autoantibody levels and demographic and behavioral data. METHODS We collected the salivary samples of patients recruited from a teaching hospital between September 2008 and December 2012. Ten salivary autoantibodies, sex, age, smoking, alcohol consumption, and betel nut chewing were used to build prediction models for identifying patients with a high risk of OSCC. The machine learning algorithms applied in the study were logistic regression, random forest, support vector machine with the radial basis function kernel, eXtreme Gradient Boosting (XGBoost), and a stacking model. We evaluated the performance of the models by using the area under the receiver operating characteristic curve (AUC), with simulations conducted 100 times. RESULTS A total of 337 participants were enrolled in this study. The best predictive model was constructed using a stacking algorithm with original forms of age and logarithmic levels of autoantibodies (AUC = 0.795 ± 0.055). Adding autoantibody levels as a data source significantly improved the prediction capability (from 0.698 ± 0.06 to 0.795 ± 0.055, p < 0.001). CONCLUSIONS We successfully established a prediction model for high-risk cases of OSCC. This model can be applied clinically through an online calculator to provide additional personalized information for OSCC diagnosis, thereby reducing the disease morbidity and mortality rates.
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Affiliation(s)
- Yi-Ju Tseng
- grid.260539.b0000 0001 2059 7017Department of Computer Science, National Yang Ming Chiao Tung University, Hsinchu, Taiwan ,grid.2515.30000 0004 0378 8438Computational Health Informatics Program, Boston Children’s Hospital, Boston, MA USA
| | - Yi-Cheng Wang
- grid.145695.a0000 0004 1798 0922Department of Information Management, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Chun Hsueh
- grid.9851.50000 0001 2165 4204Department of Fundamental Oncology, University of Lausanne, Lausanne, Switzerland ,grid.9851.50000 0001 2165 4204Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland
| | - Chih-Ching Wu
- grid.145695.a0000 0004 1798 0922Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan ,grid.145695.a0000 0004 1798 0922Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, No. 259, Wenhua 1St Rd., Guishan Dist., Taoyuan City, 33302 Taiwan ,grid.413801.f0000 0001 0711 0593Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan ,grid.145695.a0000 0004 1798 0922Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan ,grid.145695.a0000 0004 1798 0922Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Chen H, Sun G, Han Z, Wang H, Li J, Ye H, Song C, Zhang J, Wang P. Anti-CXCL8 Autoantibody: A Potential Diagnostic Biomarker for Esophageal Squamous Cell Carcinoma. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58101480. [PMID: 36295640 PMCID: PMC9607113 DOI: 10.3390/medicina58101480] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 09/15/2022] [Accepted: 10/13/2022] [Indexed: 11/07/2022]
Abstract
Background and Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Anti-tumor associated antigen autoantibodies (TAAbs) can be used as biomarkers for tumor detection. The aim of this study was to identify a reliable TAAb as the diagnostic marker for ESCC. Materials and Methods: The Cancer Genome Atlas (TCGA) database was used to screen candidate genes. The mRNA expression of the key gene was then verified by micro array dataset GSE44021 from the Gene Expression Omnibus (GEO) database and the diag nostic value of the corresponding autoantibody to the key gene in ESCC was detected by enzyme-linked im muno sorbent assay (ELISA). Results: CXCL8 was identified as the key gene. The dataset GSE44021 showed that CXCL8 mRNA expression was prominently over-expressed in ESCC tissues compared with normal tissues. ELISA results showed that the level of anti-CXCL8 autoantibody in ESCC patients was significantly higher than in normal controls and the receiver operating char ac teristic (ROC) curve indicated that anti-CXCL8 autoantibody could discriminate ESCC patients from normal controls, with the area under the ROC curve (AUC) for the verification cohort, and the validation cohort were 0.713 and 0.751, respectively. Conclusions: Our study illustrated that anti-CXCL8 autoantibody had good diagnostic value, and may become a candidate biomarker for ESCC.
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Affiliation(s)
- Huili Chen
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
| | - Guiying Sun
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
| | - Zhuo Han
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
| | - Huimin Wang
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China
| | - Jiaxin Li
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
| | - Hua Ye
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
| | - Chunhua Song
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
| | - Jianying Zhang
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China
| | - Peng Wang
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052, China
- Correspondence: ; Tel.: +86-0371-67781453
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Highly Sensitive Love Mode Acoustic Wave Platform with SiO2 Wave-Guiding Layer and Gold Nanoparticles for Detection of Carcinoembryonic Antigens. BIOSENSORS 2022; 12:bios12070536. [PMID: 35884339 PMCID: PMC9313398 DOI: 10.3390/bios12070536] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/01/2022] [Accepted: 07/14/2022] [Indexed: 11/30/2022]
Abstract
A highly sensitive and precise Love wave mode surface acoustic wave (SAW) immunosensor based on an ST-cut 90°X quartz substrate and an SiO2 wave-guiding layer was developed to detect cancer-related biomarkers of carcinoembryonic antigens (CEAs). A delay line structure of the SAW device with a resonant frequency of 196 MHz was designed/fabricated, and its surface was functionalized through CEA antibody immobilization. The CEA antibodies were bound with gold nanoparticles and CEA antibodies to form a sandwich structure, which significantly amplified the mass loading effect and enhanced the maximum responses by 30 times. The center frequency of the Love wave immunosensor showed a linear response as a function of the CEA concentration in the range of 0.2–5 ng/mL. It showed a limit of detection of 0.2 ng/mL, and its coefficient of determination was 0.983. The sensor also showed minimal interference from nonspecific adsorptions, thus demonstrating its promise for point-of-care applications for cancer biomarkers.
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Li M, Chen P, Zhao Y, Feng X, Gao S, Qi Y. Immune Infiltration Represents Potential Diagnostic and Prognostic Biomarkers for Esophageal Squamous Cell Carcinoma. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9009269. [PMID: 35795310 PMCID: PMC9251101 DOI: 10.1155/2022/9009269] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 05/19/2022] [Indexed: 12/16/2022]
Abstract
Background Immune infiltrates in the tumor microenvironment have established roles in tumor growth, invasion, and metastasis. However, the diagnostic and prognostic potential of immune cell signature in esophageal squamous cell carcinoma (ESCC) remains unclear. Results The proportions of 22 subsets of immune cells from 331 samples including 205 ESCC and 126 normal esophageal mucosa retrieved from TCGA, GEO, and GTEx databases were deciphered by CIBERSORT. Nine overlapping subsets of immune cells were identified as important features for discrimination of ESCC from normal tissue in the training cohort by LASSO and Boruta algorithms. A diagnostic immune score (DIS) developed by XGBoost showed high specificities and sensitivities in the training cohort, the internal validation cohort, and the external validation cohort (AUC: 0.999, 0.813, and 0.966, respectively). Furthermore, the prognostic immune score (PIS) was developed based on naive B cells and plasma cells using Cox proportional hazards model. The PIS, an independent prognostic predictor, classified patients with ESCC into low- and high-risk subgroups in the internal validation cohort (P = 0.038) and the external validation cohort (P = 0.022). In addition, a nomogram model comprising age, N stage, TNM stage, and PIS was constructed and performed excellent (HR = 4.17, 95% CI: 2.22-7.69, P < 0.0001) in all ESCC patients, with a time-dependent 5-year AUC of 0.745 (95% CI: 0.644 to 0.845), compared with PIS or TNM stage as a prognostic model alone. Conclusion Our DIS, PIS, and nomogram models based on infiltrated immune features may aid diagnosis and survival prediction for patients with ESCC.
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Affiliation(s)
- Mengxiang Li
- School of Information Engineering of Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang 471023, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Pan Chen
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Yuanji Zhao
- College of Biological Sciences, University of California Davis, 1 Shields Ave, Davis, CA 95616, USA
| | - Xiaoshan Feng
- School of Information Engineering of Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang 471023, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Shegan Gao
- School of Information Engineering of Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang 471023, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | - Yijun Qi
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
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Liu YQ, Chu LY, Yang T, Zhang B, Zheng ZT, Xie JJ, Xu YW, Fang WK. Serum DSG2 as a potential biomarker for diagnosis of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma. Biosci Rep 2022; 42:231196. [PMID: 35521959 PMCID: PMC9093696 DOI: 10.1042/bsr20212612] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 03/28/2022] [Accepted: 04/20/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Exploration of serum biomarkers for early detection of upper gastrointestinal cancer is required. Here, we aimed to evaluate the diagnostic potential of serum desmoglein-2 (DSG2) in patients with esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA). METHODS Serum DSG2 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 459 participants including 151 patients with ESCC, 96 with EJA, and 212 healthy controls. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. RESULTS Levels of serum DSG2 were significantly higher in patients with ESCC and EJA than those in healthy controls (P<0.001). Detection of serum DSG2 demonstrated an area under the ROC curve (AUC) value of 0.724, sensitivity of 38.1%, and specificity of 84.8% for the diagnosis of ESCC in the training cohort, and AUC 0.736, sensitivity 58.2%, and specificity 84.7% in the validation cohort. For diagnosis of EJA, measurement of DSG2 provided a sensitivity of 29.2%, a specificity of 90.2%, and AUC of 0.698. Similar results were observed for the diagnosis of early-stage ESCC (AUC 0.715 and 0.722, sensitivity 36.3 and 50%, and specificity 84.8 and 84.7%, for training and validation cohorts, respectively) and early-stage EJA (AUC 0.704, sensitivity 44.4%, and specificity 86.9%). Analysis of clinical data indicated that DSG2 levels were significantly associated with patient age and histological grade in ESCC (P<0.05). CONCLUSION Serum DSG2 may be a diagnostic biomarker for ESCC and EJA.
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Affiliation(s)
- Yin-Qiao Liu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Ling-Yu Chu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Tian Yang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Biao Zhang
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Zheng-Tan Zheng
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Wang-Kai Fang
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
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Cancer-Testis Gene Biomarkers Discovered in Colon Cancer Patients. Genes (Basel) 2022; 13:genes13050807. [PMID: 35627192 PMCID: PMC9141640 DOI: 10.3390/genes13050807] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 04/23/2022] [Accepted: 04/28/2022] [Indexed: 12/04/2022] Open
Abstract
In Saudi Arabia, colon cancer (CC) is the most prevalent cancer in men and the third most common cancer in women. Rather than being detected through screening programs, most CC cases are diagnosed mainly during clinical exams. Because of the slow growth of CC and its ability to be treated at an early stage, screening for CC can reduce the incidence of death and mortality. Consequently, there is an urgent need to identify a potential new cancer-specific biomarker for detecting early illness. Much research has been conducted on distinct antigen classes as potential new cancer-specific biomarkers for the early identification of malignancy. The cancer-testis antigens (CTAs) are one such category of antigens, with protein presence largely normally confined to human germ line cells in the testis and aberrantly produced in some cancer cells. CTAs are potentially valuable for use as cancer biomarkers and in cancer therapeutics due to their distinctive expression pattern. The aim of this current study was to identify potential cancer-testis (CT) gene biomarkers in Saudi Arabian CC patients. In this study, a total of 20 matching CC and normal colon (NC) tissues were obtained from the Saudi population. Any genes that showed expression in CC tissues but not in matching NC tissues were subsequently verified for mRNA expression in eight breast and eight leukemia malignancies using RT-PCR to determine the specificity of any CC biomarkers. CTAG1A, SPZ1, LYZL6, SCP2D1, TEX33, and TKTL2 genes were expressed in varying numbers of CC tissues compared to no measurable expressions in all NC tissue specimens, making these genes suitable potential candidates for CC markers. The most frequently expressed CT genes in CC patients were CTAG1A (35%) and SCP2D1 (35%), followed by TKTL2 (25%), SPZ1 (20%), LYZL6 (15%), and TEX33 (5%). The LYZL6 gene shows a weak RT-PCR product in 25% of breast cancer (BC) patients but not in leukemia patients. The SCP2D1 gene appears to display expression in all leukemia patients but not in the BC patients. TKTL2 expression was also observed in 50% of leukemia samples but not in the BC samples. More experiments at the protein level and with a larger cohort of patients are required to evaluate this finding.
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Al-hadlaq SM, Balto HA, Hassan WM, Marraiki NA, El-Ansary AK. Biomarkers of non-communicable chronic disease: an update on contemporary methods. PeerJ 2022; 10:e12977. [PMID: 35233297 PMCID: PMC8882335 DOI: 10.7717/peerj.12977] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 01/31/2022] [Indexed: 01/11/2023] Open
Abstract
Chronic diseases constitute a major global burden with significant impact on health systems, economies, and quality of life. Chronic diseases include a broad range of diseases that can be communicable or non-communicable. Chronic diseases are often associated with modifications of normal physiological levels of various analytes that are routinely measured in serum and other body fluids, as well as pathological findings, such as chronic inflammation, oxidative stress, and mitochondrial dysfunction. Identification of at-risk populations, early diagnosis, and prediction of prognosis play a major role in preventing or reducing the burden of chronic diseases. Biomarkers are tools that are used by health professionals to aid in the identification and management of chronic diseases. Biomarkers can be diagnostic, predictive, or prognostic. Several individual or grouped biomarkers have been used successfully in the diagnosis and prediction of certain chronic diseases, however, it is generally accepted that a more sophisticated approach to link and interpret various biomarkers involved in chronic disease is necessary to improve our current procedures. In order to ensure a comprehensive and unbiased coverage of the literature, first a primary frame of the manuscript (title, headings and subheadings) was drafted by the authors working on this paper. Second, based on the components drafted in the preliminary skeleton a comprehensive search of the literature was performed using the PubMed and Google Scholar search engines. Multiple keywords related to the topic were used. Out of screened papers, only 190 papers, which are the most relevant, and recent articles were selected to cover the topic in relation to etiological mechanisms of different chronic diseases, the most recently used biomarkers of chronic diseases and finally the advances in the applications of multivariate biomarkers of chronic diseases as statistical and clinically applied tool for the early diagnosis of chronic diseases was discussed. Recently, multivariate biomarkers analysis approach has been employed with promising prospect. A brief discussion of the multivariate approach for the early diagnosis of the most common chronic diseases was highlighted in this review. The use of diagnostic algorithms might show the way for novel criteria and enhanced diagnostic effectiveness inpatients with one or numerous non-communicable chronic diseases. The search for new relevant biomarkers for the better diagnosis of patients with non-communicable chronic diseases according to the risk of progression, sickness, and fatality is ongoing. It is important to determine whether the newly identified biomarkers are purely associations or real biomarkers of underlying pathophysiological processes. Use of multivariate analysis could be of great importance in this regard.
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Affiliation(s)
- Solaiman M. Al-hadlaq
- Department of Restorative Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Hanan A. Balto
- Department of Restorative Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia,Central Research Laboratory, Female Campus, King Saud University, Riyadh, Saudi Arabia
| | - Wail M. Hassan
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, KS, United States of America
| | - Najat A. Marraiki
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Afaf K. El-Ansary
- Central Research Laboratory, Female Campus, King Saud University, Riyadh, Saudi Arabia
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22
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Samiei H, Ajam F, Gharavi A, Abdolmaleki S, Kokhaei P, Mohammadi S, Memarian A. Simultaneous disruption of circulating miR-21 and cytotoxic T lymphocytes (CTLs): Prospective diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). J Clin Lab Anal 2022; 36:e24125. [PMID: 34799871 PMCID: PMC8761409 DOI: 10.1002/jcla.24125] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/06/2021] [Accepted: 11/09/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) as the most prominent type of esophageal cancer (EC) in developing countries encompasses a substantial contribution of cancer-related mortalities and morbidities. Cytotoxic T lymphocytes (CTLs) are the major subset of effector T cells against cancer. However, the microRNAs involved in the development and regulation of CTLs could be disrupted in cancers such as EC. METHODS Here, we evaluated the population of IL-10, TGF-β, IFN-γ, and IL-17a-producing CD3+CD8+ T cells, their association with the circulating levels of miR-21 and miR-29b, and their diagnostic and/or prognostic (after 160 weeks of follow-up) utilities in 34 ESCC patients (12 newly diagnosed: ND, 24 under-treatment: UT) and 34 matched healthy donors. RESULTS The population of IL-10 and TGF-β-producing CTLs (CD8+ Tregs) were considerably expanded, in addition to the overexpression of miR-21 in both groups (ND and UT) of ESCC patients, while the frequency of Tc17 and CD8+ Treg cells increased only in UT patients. The expression means of TGF-β and IL-10 in CTLs were considered to be excellent biomarkers (1 ≥ area under the curve: AUC ≥0.9) in distinguishing ESCC patients and associated subgroups from healthy subjects. Moreover, the lower expressions of TGF-β, IL-17a, IL-10, and IFN-γ in CTLs were associated with ESCC better prognosis. CONCLUSIONS The association between the impaired function of CD3+ CD8+ T cell subsets and miR-21 expression could be introduced as novel therapeutic targets and powerful diagnostic and prognostic markers for ESCC.
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Affiliation(s)
- Hadiseh Samiei
- Immunology DepartmentFaculty of MedicineSemnan University of Medical SciencesSemnanIran
| | - Faezeh Ajam
- Immunology DepartmentFaculty of MedicineGolestan University of Medical SciencesGorganIran
| | - Abdolsamad Gharavi
- Digestive Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Golestan Research Center of Gastroenterology and HepatologyGolestan University of Medical SciencesGorganIran
| | - Sara Abdolmaleki
- Clinical Immunology LaboratoryDeziani Specialized and Advanced ClinicGolestan University of Medical SciencesGorganIran
| | - Parviz Kokhaei
- Immune and Gene Therapy LaboratoryCancer Centre KarolinskaDepartment of Oncology and PathologyKarolinska InstituteStockholmSweden
- Cancer Research Center and Department of ImmunologySemnan University of Medical SciencesSemnanIran
| | - Saeed Mohammadi
- Stem Cell Research CenterGolestan University of Medical SciencesGorganIran
- Infectious Diseases Research CenterGolestan University of Medical SciencesGorganIran
| | - Ali Memarian
- Golestan Research Center of Gastroenterology and HepatologyGolestan University of Medical SciencesGorganIran
- Department of ImmunologySchool of MedicineGolestan University of Medical SciencesGorganIran
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Wang M, Liu F, Pan Y, Xu R, Li F, Liu A, Yang H, Duan L, Shen L, Wu Q, Liu Y, Liu M, Liu Z, Hu Z, Chen H, Cai H, He Z, Ke Y. Tumor-associated autoantibodies in ESCC screening: Detecting prevalent early-stage malignancy or predicting future cancer risk? EBioMedicine 2021; 73:103674. [PMID: 34753106 PMCID: PMC8586741 DOI: 10.1016/j.ebiom.2021.103674] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/19/2021] [Accepted: 10/19/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND To assess potential roles for tumor-associated autoantibodies (TAAs) in esophageal squamous cell carcinoma (ESCC) screening: detecting early-stage malignancy, and predicting future cancer risk. METHOD Thirteen candidate autoantibodies identified in previous literatures were measured using multiplex serological assays in sera from cases and matched controls nested in two population-level screening cohorts in China. To evaluate the role of TAAs in detecting prevalent esophageal malignant lesions, an identification set (150 cases vs. 560 controls) and an external validation set (34 cases vs. 121 controls) were established with pre-screening sera collected ≤ 12 months prior to screening-related diagnosis. To explore the role of TAAs in predicting future ESCC risk, an exploration set (105 cases vs. 416 controls) with pre-diagnostic sera collected > 12 months before clinical diagnosis was established. Two models, the questionnaire-based model and full model additionally incorporating TAA markers, were constructed. Area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to compare the performance of the two models. FINDINGS In the identification set, NY-ESO-1 (OR=2·12, 95% CI=1·02-4·40) and STIP1 (OR=1·83, 95% CI=1·10-3·05) were positively associated with higher risk of esophageal malignancy. Elevated MMP-7 was associated with higher risk of malignancy in females (ORfemale=5·07, 95% CI=1·30-19·71). The estimates in validation set were consistent with these results, but were close to null in exploration set. Integration of selected TAAs improved the performance of questionnaire-based models in detecting prevalent esophageal malignancy (female: AUCfull model=0·745, 95% CI=0·675-0·814, AUCquestionnaire-based model=0·658, 95% CI=0·585-0·732, NRI=0·604, P<0·0001; male: AUCfull model=0·662, 95% CI=0·596-0·728, AUCquestionnaire-based model=0·619, 95% CI=0·548-0·690, NRI=0·357, P=0·0028). This improvement was also seen in validation set, but was not similarly effective in distinguishing long-term incident cases from healthy controls. INTERPRETATION Serological autoantibodies against NY-ESO-1, STIP1, and MMP-7 perform well in detecting early-stage esophageal malignancy, but are less effective in predicting future ESCC risks. FUNDING This work was supported by the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Natural Science Foundation of China (82073626), the National Key R&D Program of China (2016YFC0901404), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204), and the Natural Science Foundation of Beijing Municipality (7182033).
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Affiliation(s)
- Minmin Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Fangfang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Yaqi Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Ruiping Xu
- Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Fenglei Li
- Hua County People's Hospital, Anyang, Henan Province, P.R. China
| | - Anxiang Liu
- Endoscopy center, Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Haijun Yang
- Department of pathology, Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P.R. China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Qi Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Endoscopy Center, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Ying Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Mengfei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhen Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhe Hu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Huanyu Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Hong Cai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhonghu He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
| | - Yang Ke
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
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Wang H, Yang X, Sun G, Yang Q, Cui C, Wang X, Ye H, Dai L, Shi J, Zhang J, Wang P. Identification and Evaluation of Autoantibody to a Novel Tumor-Associated Antigen GNA11 as a Biomarker in Esophageal Squamous Cell Carcinoma. Front Oncol 2021; 11:661043. [PMID: 34568004 PMCID: PMC8462091 DOI: 10.3389/fonc.2021.661043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 08/18/2021] [Indexed: 12/15/2022] Open
Abstract
The study aims to explore the diagnostic value of anti-GNA11 autoantibody in esophageal squamous cell carcinoma (ESCC) from multiple levels. Autoantibody against GNA11 with the highest diagnostic performance was screened out from the customized protein microarray. A total of 486 subjects including ESCC patients and matched normal controls were recruited in the verification and validation phases by using enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was used to verify the ELISA results. Immunohistochemistry (IHC) was used to evaluate GNA11 expression in ESCC tissues and para-tumor tissues. In addition, a bioinformatics approach was adopted to investigate the mRNA expression of GNA11 in ESCC. Results indicated that the level of anti-GNA11 autoantibody in ESCC patients was significantly higher than that in the normal controls, and it can be used to distinguish ESCC patients from normal individuals in clinical subgroups (p < 0.05), as revealed by both ELISA and Western blotting. The receiver operating characteristic (ROC) curve analysis showed that anti-GNA11 autoantibody could distinguish ESCC patients from normal controls with an area under the ROC curve (AUC) of 0.653, sensitivity of 10.96%, and specificity of 98.63% in the verification cohort and with an AUC of 0.751, sensitivity of 38.24%, and specificity of 88.82% in the validation cohort. IHC manifested that the expression of GNA11 can differentiate ESCC tissues with para-tumor tissues (p < 0.05), but it cannot be used to differentiate different pathological grades and clinical stages (p > 0.05). The mRNA expression of GNA11 in ESCC patients and normal controls was different with a bioinformatics mining with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data in Gene Expression Profiling Interactive Analysis (GEPIA). In summary, anti-GNA11 autoantibody has the potential to be a new serological marker in the diagnosis of ESCC.
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Affiliation(s)
- Huimin Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiaoang Yang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China
| | - Guiying Sun
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Qian Yang
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Chi Cui
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Xiao Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Hua Ye
- Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Jianxiang Shi
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Jianying Zhang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China
| | - Peng Wang
- Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China.,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.,College of Public Health, Zhengzhou University, Zhengzhou, China
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Chang C, Wang MJ, Bi XF, Fan ZY, Feng D, Cai HQ, Zhang Y, Xu X, Cai Y, Qi J, Wei WQ, Hao JJ, Wang MR. Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma. J Clin Lab Anal 2021; 35:e23904. [PMID: 34288108 PMCID: PMC8418505 DOI: 10.1002/jcla.23904] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/29/2021] [Accepted: 06/30/2021] [Indexed: 12/30/2022] Open
Abstract
Background and Aims Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. Methods In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL‐2, IL‐5, IP‐10, IL‐8, eotaxin, TNF‐α, HGF, and MIP‐1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. Results In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP‐10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early‐stage (0‐IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21‐1 (in use clinically) with eotaxin or IP‐10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21‐1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). Conclusions The data suggest that serum eotaxin and IP‐10 might be potential biomarkers for the detection of ESCC.
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Affiliation(s)
- Chen Chang
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min-Jie Wang
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao-Feng Bi
- Department of Cancer Prevention, Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhi-Yuan Fan
- Department of Cancer Epidemiology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dan Feng
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong-Qing Cai
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Zhang
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Xu
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Cai
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Qi
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen-Qiang Wei
- Department of Cancer Epidemiology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jia-Jie Hao
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming-Rong Wang
- State Key Laboratory of Molecular Oncology, Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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26
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Yang SH, Liu CT, Hong CQ, Huang ZY, Wang HZ, Wei LF, Lin YW, Guo HP, Peng YH, Xu YW. Autoantibodies against p53, MMP-7, and Hsp70 as Potential Biomarkers for Detection of Nonmelanoma Skin Cancers. DISEASE MARKERS 2021; 2021:5592693. [PMID: 34336006 PMCID: PMC8289574 DOI: 10.1155/2021/5592693] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 05/31/2021] [Indexed: 02/05/2023]
Abstract
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are two predominant histological types of nonmelanoma skin cancer (NMSC), lacking effective early diagnostic markers. In this study, we assessed the diagnostic value of autoantibodies against p53, MMP-7, and Hsp70 in skin SCC and BCC. ELISA was performed to detect levels of autoantibodies in sera from 101 NMSC patients and 102 normal controls, who were recruited from the Cancer Hospital of Shantou University Medical College. A receiver operator characteristic curve was used to evaluate the diagnostic value. The serum levels of autoantibodies against p53, MMP-7, and Hsp70 were higher in NMSCs than those in the normal controls (all P < 0.01). The AUC of the three-autoantibody panel was 0.841 (95% CI: 0.788-0.894) with the sensitivity and specificity of 60.40% and 91.20% when differentiating NMSCs from normal controls. Furthermore, measurement of this panel could differentiate early-stage skin cancer patients from normal controls (AUC: 0.851; 95% CI: 0.793-0.908). Data from Oncomine showed that the level of p53 mRNA was elevated in BCC (P < 0.05), and the Hsp70 mRNA was upregulated in SCC (P < 0.001). This serum three-autoantibody panel might function in assisting the early diagnosis of NMSC.
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Affiliation(s)
- Shi-Han Yang
- Department of Dermatology and Venereology, Affiliated Shantou Hospital of Sun Yat-sen University, 114 Waima Road, Shantou 515041, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Chao-Qun Hong
- Department of Oncological Laboratory Research, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
| | - Ze-Yuan Huang
- Department of Dermatology and Venereology, Affiliated Shantou Hospital of Sun Yat-sen University, 114 Waima Road, Shantou 515041, China
| | - Huan-Zhu Wang
- Department of Dermatology and Venereology, Affiliated Shantou Hospital of Sun Yat-sen University, 114 Waima Road, Shantou 515041, China
| | - Lai-Feng Wei
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Yi-Wei Lin
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Hai-Peng Guo
- Department of Head and Neck Surgery, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515041, China
- Precision Medicine Research Center, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, 22 Xinling Road, Shantou 515041, China
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27
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Visaggi P, Barberio B, Ghisa M, Ribolsi M, Savarino V, Fassan M, Valmasoni M, Marchi S, de Bortoli N, Savarino E. Modern Diagnosis of Early Esophageal Cancer: From Blood Biomarkers to Advanced Endoscopy and Artificial Intelligence. Cancers (Basel) 2021; 13:3162. [PMID: 34202763 PMCID: PMC8268190 DOI: 10.3390/cancers13133162] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 12/16/2022] Open
Abstract
Esophageal cancer (EC) is the seventh most common cancer and the sixth cause of cancer death worldwide. Histologically, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) account for up to 90% and 20% of all ECs, respectively. Clinical symptoms such as dysphagia, odynophagia, and bolus impaction occur late in the natural history of the disease, and the diagnosis is often delayed. The prognosis of ESCC and EAC is poor in advanced stages, being survival rates less than 20% at five years. However, when the diagnosis is achieved early, curative treatment is possible, and survival exceeds 80%. For these reasons, mass screening strategies for EC are highly desirable, and several options are currently under investigation. Blood biomarkers offer an inexpensive, non-invasive screening strategy for cancers, and novel technologies have allowed the identification of candidate markers for EC. The esophagus is easily accessible via endoscopy, and endoscopic imaging represents the gold standard for cancer surveillance. However, lesion recognition during endoscopic procedures is hampered by interobserver variability. To fill this gap, artificial intelligence (AI) has recently been explored and provided encouraging results. In this review, we provide a summary of currently available options to achieve early diagnosis of EC, focusing on blood biomarkers, advanced endoscopy, and AI.
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Affiliation(s)
- Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (P.V.); (S.M.); (N.d.B.)
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (B.B.); (M.G.)
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (B.B.); (M.G.)
| | - Mentore Ribolsi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, 00128 Roma, Italy;
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16143 Genoa, Italy;
| | - Matteo Fassan
- Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy;
| | - Michele Valmasoni
- Department of Surgical, Oncological and Gastroenterological Sciences, Center for Esophageal Disease, University of Padova, 35124 Padova, Italy;
| | - Santino Marchi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (P.V.); (S.M.); (N.d.B.)
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (P.V.); (S.M.); (N.d.B.)
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35121 Padua, Italy; (B.B.); (M.G.)
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28
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Hong CQ, Weng XF, Huang XC, Chu LY, Wei LF, Lin YW, Chen LY, Liu CT, Xu YW, Peng YH. A Panel of Tumor-associated Autoantibodies for the Detection of Early-stage Breast Cancer. J Cancer 2021; 12:2747-2755. [PMID: 33854634 PMCID: PMC8040727 DOI: 10.7150/jca.57019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 01/22/2021] [Indexed: 02/07/2023] Open
Abstract
We previously found a panel of autoantibodies against multiple tumor-associated antigens (BMI-1, HSP70, MMP-7, NY-ESO-1, p53 and PRDX6) that might facilitate early detection of esophagogastric junction adenocarcinoma and esophageal squamous cell carcinoma. Here we aimed at assessing the diagnostic performance of these autoantibodies in breast cancer patients. Enzyme-linked immunosorbent assay was applied to detect sera autoantibodies in 123 breast cancer patients and 123 age-matched normal controls. We adopted logistic regression analysis to identify optimized autoantibody biomarkers for diagnosis and receiver-operating characteristics to analyze diagnostic efficiency. Five of six autoantibodies, BMI-1, HSP70, NY-ESO-1, p53 and PRDX6 demonstrated significantly elevated serum levels in breast cancer compared to normal controls. An optimized panel composed of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 showed an area under the curve (AUC) of 0.819 (95% CI 0.766-0.873), 63.4% sensitivity and 90.2% specificity for diagnosing breast cancer. Moreover, this autoantibody panel could differentiate patients with early stage breast cancer from normal controls, with AUC of 0.805 (95% CI 0.743-0.886), 59.6% sensitivity and 90.2% specificity. Our findings indicated that the panel of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 as serum biomarkers have the potential to help detect early stage breast cancer.
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Affiliation(s)
- Chao-Qun Hong
- Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xue-Fen Weng
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xu-Chun Huang
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Ling-Yu Chu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Lai-Feng Wei
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yi-Wei Lin
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Liu-Yi Chen
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yi-Wei Xu
- Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yu-Hui Peng
- Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou 515041, Guangdong, China
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29
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Yang X, Suo C, Zhang T, Yin X, Man J, Yuan Z, Yu J, Jin L, Chen X, Lu M, Ye W. Targeted proteomics-derived biomarker profile develops a multi-protein classifier in liquid biopsies for early detection of esophageal squamous cell carcinoma from a population-based case-control study. Biomark Res 2021; 9:12. [PMID: 33597040 PMCID: PMC7890600 DOI: 10.1186/s40364-021-00266-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 02/04/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for the early detection of ESCC. METHODS We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. RESULTS We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early-stage ESCC from healthy controls, which were validated by the significant dose-response relationships with ESCC pathological progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14 (kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in the final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899 ~ 0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. CONCLUSIONS Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC, especially with the establishment of a three-level hierarchical screening strategy for ESCC control.
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Affiliation(s)
- Xiaorong Yang
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.,Clinical Research Center of Shandong University, Qilu Hospital of Shandong University, Jinan, China
| | - Chen Suo
- Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Shanghai, China
| | - Tongchao Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China
| | - Xiaolin Yin
- Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China
| | - Jinyu Man
- Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, China
| | - Ziyu Yuan
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Jingru Yu
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Li Jin
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China. .,State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai, 200438, China.
| | - Ming Lu
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China. .,Clinical Research Center of Shandong University, Qilu Hospital of Shandong University, Jinan, China. .,Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
| | - Weimin Ye
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
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30
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Calanzani N, Druce PE, Snudden C, Milley KM, Boscott R, Behiyat D, Saji S, Martinez-Gutierrez J, Oberoi J, Funston G, Messenger M, Emery J, Walter FM. Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review. Adv Ther 2021; 38:793-834. [PMID: 33306189 PMCID: PMC7889689 DOI: 10.1007/s12325-020-01571-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 11/11/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. METHODS We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes. RESULTS We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively. CONCLUSION Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended.
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Affiliation(s)
- Natalia Calanzani
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
| | - Paige E Druce
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Claudia Snudden
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Kristi M Milley
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Rachel Boscott
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Dawnya Behiyat
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Smiji Saji
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Javiera Martinez-Gutierrez
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
- Department of Family Medicine, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Jasmeen Oberoi
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Garth Funston
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Mike Messenger
- Leeds Centre for Personalised Medicine and Health, University of Leeds, Leeds, UK
| | - Jon Emery
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Fiona M Walter
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
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31
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Yajima S, Suzuki T, Oshima Y, Shiratori F, Funahashi K, Kawai S, Nanki T, Muraoka S, Urita Y, Saida Y, Okazumi S, Kitagawa Y, Hirata Y, Hasegawa H, Okabayashi K, Murakami M, Yamashita T, Kato R, Matsubara H, Murakami K, Nakajima Y, Sugita H, Klammer M, Shimada H. New Assay System Elecsys Anti-p53 to Detect Serum Anti-p53 Antibodies in Esophageal Cancer Patients and Colorectal Cancer Patients: Multi-institutional Study. Ann Surg Oncol 2020; 28:4007-4015. [PMID: 33210269 DOI: 10.1245/s10434-020-09342-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 10/20/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). METHODS Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. RESULTS Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 μg/mL (range < 0.02-29.2 μg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 μg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer. CONCLUSIONS The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates.
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Affiliation(s)
- Satoshi Yajima
- Department of Surgery, School of Medicine, Toho University, Tokyo, Japan
| | - Takashi Suzuki
- Department of Surgery, School of Medicine, Toho University, Tokyo, Japan
| | - Yoko Oshima
- Department of Surgery, School of Medicine, Toho University, Tokyo, Japan
| | - Fumiaki Shiratori
- Department of Surgery, School of Medicine, Toho University, Tokyo, Japan
| | - Kimihiko Funahashi
- Department of Surgery, School of Medicine, Toho University, Tokyo, Japan
| | - Shinichi Kawai
- Department of Inflammation and Pain Control Research, School of Medicine, Toho University, Tokyo, Japan
| | - Toshihiro Nanki
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Toho University, Tokyo, Japan
| | - Sei Muraoka
- Division of Rheumatology, Department of Internal Medicine, School of Medicine, Toho University, Tokyo, Japan
| | - Yoshihisa Urita
- General Medicine and Emergency Center, School of Medicine, Toho University, Tokyo, Japan
| | - Yoshihisa Saida
- Department of Surgery, Ohashi Medical Center, Toho University, Tokyo, Japan
| | - Shinichi Okazumi
- Department of Surgery, Sakura Medical Center, Toho University, Tokyo, Japan
| | - Yuko Kitagawa
- Department of General and Gastroenterological Surgery, Keio University Hospital, Tokyo, Japan
| | - Yuki Hirata
- Department of General and Gastroenterological Surgery, Keio University Hospital, Tokyo, Japan
| | - Hirotoshi Hasegawa
- Department of General and Gastroenterological Surgery, Keio University Hospital, Tokyo, Japan
| | - Koji Okabayashi
- Department of General and Gastroenterological Surgery, Keio University Hospital, Tokyo, Japan
| | | | | | - Rei Kato
- Department of Surgery, Showa University Hospital, Tokyo, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kentaro Murakami
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasuaki Nakajima
- Esophageal Surgery, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan
| | | | - Martin Klammer
- Department of Biostatistics and Advanced Data Analytics, Roche Diagnostics GmbH, Penzberg, Germany
| | - Hideaki Shimada
- Department of Surgery, School of Medicine, Toho University, Tokyo, Japan. .,Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, Tokyo, Japan.
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Hoshino I, Nabeya Y, Takiguchi N, Gunji H, Ishige F, Iwatate Y, Kuwajima A, Shiratori F, Okada R, Shimada H. Inducing multiple antibodies to treat squamous cell esophageal carcinoma. BMC Cancer 2020; 20:1007. [PMID: 33069225 PMCID: PMC7568359 DOI: 10.1186/s12885-020-07466-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 09/28/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The positive response and the clinical usefulness of 14 serum antibodies in patients with esophageal squamous cell carcinoma (ESCC) were examined in this study. The Cancer Genome Atlas (TCGA) was used to investigate the frequency of gene expressions, mutations, and amplification of these 14 antigens and also the possible effects of antibody induction. METHODS Blood serum derived from 85 patients with ESCC was collected and analyzed for the 14 antibodies using ELISA. The prognosis between positive and negative antibodies were then compared. The antibody panel included LGALS1, HCA25a, HCC-22-5, and HSP70. RESULTS Patient serum was positive for all antibodies, except VEGF, with the positive rates ranging from 1.18 to 10.59%. Positive rates for LGALS1, HCA25a, HCC-22-5, and HSP70 were > 10%. TCGA data revealed that all antigen-related genes had little or no mutation or amplification, and hence an increase in gene expression affected antibody induction. The positive results from the panel accounted for the positive rate comparable to the combination of CEA and SCC. No significant association was observed between the presence of antibodies and disease prognosis. CONCLUSIONS The detection rates of LGALS1, HCA25a, HCC-22-5, and HSP70 were 10% higher in patients with ESCC. Gene overexpression may be involved in such antibody production. These four antibodies were applied as a panel in comparison with conventional tumor markers. Moreover, it was confirmed that the combination of this panel and the conventional tumor markers significantly improved the positive rate.
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Affiliation(s)
- Isamu Hoshino
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan.
| | - Yoshihiro Nabeya
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan
| | - Nobuhiro Takiguchi
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan
| | - Hisashi Gunji
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan
| | - Fumitaka Ishige
- Department of Hepatobiliary and Pancreatic Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, Japan
| | - Yosuke Iwatate
- Department of Hepatobiliary and Pancreatic Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, Japan
| | - Akiko Kuwajima
- Medical & Biological Laboratories Co., Ltd, 4-5-3 Sakae, Naka-ku, Nagoya, 460-0008, Japan
| | - Fumiaki Shiratori
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan.,Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Rei Okada
- Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Hideaki Shimada
- Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
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Feng Y, Xia W, He G, Ke R, Liu L, Xie M, Tang A, Yi X. Accuracy Evaluation and Comparison of 14 Diagnostic Markers for Nasopharyngeal Carcinoma: A Meta-Analysis. Front Oncol 2020; 10:1779. [PMID: 33072558 PMCID: PMC7531263 DOI: 10.3389/fonc.2020.01779] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 08/11/2020] [Indexed: 12/14/2022] Open
Abstract
The aim of the present study was to collect published studies and compare the diagnostic accuracy of different markers for nasopharyngeal carcinoma (NPC). We systematically searched PubMed/MEDLINE, EMBASE, Cochrane Library, CNKI, and Wanfang for relevant studies until April 29, 2020. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the methodological quality of the studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) values of the diagnostic markers were combined by a bivariate mixed effect model to compare their diagnostic accuracy. We explored heterogeneity through meta-regression. In total, 244 records from 101 articles were included, with 49,432 total study subjects (13,109 cases and 36,323 controls). EA-IgG, Zta-IgG, and Epstein-Barr virus (EBV) DNA load in non-invasive nasopharyngeal brushings (EBV-DNA brushings) have both high sensitivity and specificity, EBNA1-IgG and VCA-IgG have only high sensitivity, and EBNA1-IgA, VCA-IgA, Rta-IgG, Zta-IgA, HSP70, and serum sialic acid (SA) have only high specificity. The bivariate mixed effect model of EA-IgA had a significant threshold effect. Meta-regression analysis showed that ethnicity affected EBNA1-IgA, EBNA1-IgG, VCA-IgA, and EBV DNA load in plasma, test methods affected EBNA1-IgG, publication year affected VCA-IgA, and sample size affected Rta-IgG. There was significant publication bias for VCA-IgA and Rta-IgG (P < 0.05). EA-IgG, Zta-IgG, and EBV-DNA brushings are good diagnostic markers for NPC. The diagnostic accuracy was influenced by publication year, sample size, test methods, and ethnicity.
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Affiliation(s)
- Yiwei Feng
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- First Clinical Medical College, Guangxi Medical University, Nanning, China
| | - Wei Xia
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- First Clinical Medical College, Guangxi Medical University, Nanning, China
| | - Guangyao He
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Rongdan Ke
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lei Liu
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Mao Xie
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Anzhou Tang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiang Yi
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, China
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Sun G, Ye H, Wang X, Cheng L, Ren P, Shi J, Dai L, Wang P, Zhang J. Identification of novel autoantibodies based on the protein chip encoded by cancer-driving genes in detection of esophageal squamous cell carcinoma. Oncoimmunology 2020; 9:1814515. [PMID: 33457096 PMCID: PMC7781740 DOI: 10.1080/2162402x.2020.1814515] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 08/03/2020] [Accepted: 08/20/2020] [Indexed: 01/22/2023] Open
Abstract
The purpose of this study was to identify novel autoantibodies against tumor-associated antigens (TAAbs) and explore the optimal diagnosis model based on the protein chip for detecting esophageal squamous cell carcinoma (ESCC). The human protein chip based on cancer-driving genes was customized to discover candidate TAAbs. Enzyme-linked immunosorbent assay was applied to verify and validate the expression levels of candidate TAAbs in the training cohort (130 ESCC and 130 normal controls) and the validation cohort (125 ESCC and 125 normal controls). Logistic regression analysis was adopted to construct the diagnostic model based on the expression levels of autoantibodies with diagnostic value. Twelve candidate autoantibodies were identified based on the protein chip according to the corresponding statistical methods. In both the training cohort and validation cohort, the expression levels of 10 TAAbs (GNA11, PTEN, P53, SRSF2, GNAS, ACVR1B, CASP8, DAXX, PDGFRA, and MEN1) in ESCC patients were higher than that in normal controls. The panel consisting of GNA11, ACVR1B and P53 demonstrated favorable diagnostic power. The sensitivity, specificity and accuracy of the model in the train cohort and the validation cohort were 71.5%, 93.8%, 79.6% and 77.6%, 81.6%, 70.8%, respectively. In either cohort, there was no correlation between positive rate of the autoantibody panel and clinicopathologic features for ESCC patients. Protein chip technology is an effective method to identify novel TAAbs, and the panel of 3 TAAbs (GNA11, ACVR1B, and P53) is promising for distinguishing ESCC patients from normal individuals.
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Affiliation(s)
- Guiying Sun
- College of Public Health, Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China
| | - Hua Ye
- College of Public Health, Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China
| | - Xiao Wang
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Lin Cheng
- College of Life Science, Xinyang Normal University, Xinyang, China
| | - Pengfei Ren
- Department of Molecular Pathology& Henan Key Laboratory of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianxiang Shi
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Liping Dai
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China
| | - Jianying Zhang
- College of Public Health, Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
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Bmi1 Severs as a Potential Tumor-Initiating Cell Marker and Therapeutic Target in Esophageal Squamous Cell Carcinoma. Stem Cells Int 2020; 2020:8877577. [PMID: 32884573 PMCID: PMC7455816 DOI: 10.1155/2020/8877577] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/06/2020] [Accepted: 06/10/2020] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a frequent malignant tumor with low 5-year overall survival. Targeting ESCC tumor-initiating cells (TICs) may provide a new research avenue to achieve better therapeutic effects of ESCC. However, the identity and characteristics of ESCC TICs remain poorly understood. Through genetic lineage tracing approach, we found that a group of Moloney murine leukemia virus insertion site 1- (Bmi1-) expressing cell populations present in the invasive front of the esophageal epithelium, providing a continuous flow of tumor cells for ESCC. Subsequently, we found that ablation of Bmi1+ cells from mice with ESCC led to inhibition of tumor growth. In addition, our results demonstrated that PTC-209, an inhibitor of Bmi1, was able to inhibit ESCC progression when combined with cisplatin. In summary, our data suggest that Bmi1+ cells serve as TICs in ESCC.
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Zhang S, Liu Y, Chen J, Shu H, Shen S, Li Y, Lu X, Cao X, Dong L, Shi J, Cao Y, Wang X, Zhou J, Liu Y, Chen L, Fan J, Ding G, Gao Q. Autoantibody signature in hepatocellular carcinoma using seromics. J Hematol Oncol 2020; 13:85. [PMID: 32616055 PMCID: PMC7330948 DOI: 10.1186/s13045-020-00918-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 06/16/2020] [Indexed: 02/07/2023] Open
Abstract
Background Alpha-fetoprotein (AFP) is a widely used biomarker for hepatocellular carcinoma (HCC) early detection. However, low sensitivity and false negativity of AFP raise the requirement of more effective early diagnostic approaches for HCC. Methods We employed a three-phase strategy to identify serum autoantibody (AAb) signature for HCC early diagnosis using protein array-based approach. A total of 1253 serum samples from HCC, liver cirrhosis, and healthy controls were prospectively collected from three liver cancer centers in China. The Human Proteome Microarray, comprising 21,154 unique proteins, was first applied to identify AAb candidates in discovery phase (n = 100) and to further fabricate HCC-focused arrays. Then, an artificial neural network (ANN) model was used to discover AAbs for HCC detection in a test phase (n = 576) and a validation phase (n = 577), respectively. Results Using HCC-focused array, we identified and validated a novel 7-AAb panel containing CIAPIN1, EGFR, MAS1, SLC44A3, ASAH1, UBL7, and ZNF428 for effective HCC detection. The ANN model of this panel showed improvement of sensitivity (61.6–77.7%) compared to AFP (cutoff 400 ng/mL, 28.4–30.7%). Notably, it was able to detect AFP-negative HCC with AUC values of 0.841–0.948. For early-stage HCC (BCLC 0/A) detection, it outperformed AFP (cutoff 400 ng/mL) with approximately 10% increase in AUC. Conclusions The 7-AAb panel provides potentially clinical value for non-invasive early detection of HCC, and brings new clues on understanding the immune response against hepatocarcinogenesis.
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Affiliation(s)
- Shu Zhang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
| | - Yuming Liu
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
| | - Jing Chen
- The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Hong Shu
- Department of Clinical Laboratory, Cancer Hospital of Guangxi Medical University, Nanning, 530021, China
| | - Siyun Shen
- The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Yin Li
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Xinyuan Lu
- The Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Xinyi Cao
- Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Liangqing Dong
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
| | - Jieyi Shi
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
| | - Ya Cao
- Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital and Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, 410078, China
| | - Xiaoying Wang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
| | - Yinkun Liu
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Lei Chen
- The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Guangyu Ding
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China.
| | - Qiang Gao
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China. .,Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
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Tumor-associated antigens and their antibodies in the screening, diagnosis, and monitoring of esophageal cancers. Eur J Gastroenterol Hepatol 2020; 32:779-788. [PMID: 32243347 DOI: 10.1097/meg.0000000000001718] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Despite the advances in the treatment and management, esophageal cancers continue to carry a dismal prognosis with an overall 5-year survival rate ranging from 15 to 25%. Delayed onset of symptoms and lack of effective screening methods and guidelines for diagnosis of the early disease contribute to the high mortality rate of esophageal cancers. Detection of esophageal cancer at their early stage is really a challenge for physicians including primary care physicians, gastroenterologists and oncologists. Although imaging, endoscopy and biopsy have been proved to be useful diagnostic tools for esophageal cancers, their diagnostic accuracy is unsatisfactory. In addition, expensive costs, invasiveness and special training operator have limited the clinical application of these tools. Recently, tumor-associated antigens (TAAs) and their antibodies have been reported to be potential markers in esophageal cancer screening, diagnosis, monitoring and prognostication. Because TAAs and their antibodies have the advantages of inexpensive cost, noninvasiveness and easy access, they have attracted much attention as an affordable option for early esophageal cancer diagnosis. In this review, we summarized the advances in TAAs and their antibodies in esophageal cancer screening, diagnosis, monitoring and prognostication.
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Chu LY, Peng YH, Weng XF, Xie JJ, Xu YW. Blood-based biomarkers for early detection of esophageal squamous cell carcinoma. World J Gastroenterol 2020; 26:1708-1725. [PMID: 32351288 PMCID: PMC7183865 DOI: 10.3748/wjg.v26.i15.1708] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 03/13/2020] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present, early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a non-invasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC. This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.
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Affiliation(s)
- Ling-Yu Chu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Xue-Fen Weng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou 515041, Guangdong Province, China
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Li M, Wang K, Pang Y, Zhang H, Peng H, Shi Q, Zhang Z, Cui X, Li F. Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1) Are Associated with Progression and Prognosis of Esophageal Cancer as Identified by Integrated Expression Profiles Analysis. Med Sci Monit 2020; 26:e920355. [PMID: 32208405 PMCID: PMC7111131 DOI: 10.12659/msm.920355] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Esophageal cancer is a malignant tumor with a complex pathogenesis and a poor 5-year survival rate, which encourages researchers to explore its molecular mechanisms deeper to improve the prognosis. Material/Methods DEGs were from 4 Gene Expression Omnibus (GEO) databases (GSE92396, GSE20347, GSE23400, and GSE45168) including 87 esophageal tumor samples and 84 normal samples. We performed Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Protein-Protein interaction (PPI) analysis, and GeneMANIA to identify the DEGs. Gene set enrichment analysis (GSEA) and Kaplan-Meier survival analyses were performed. Results There was an overlapping subset consisting of 120 DEGs that was present in all esophageal tumor samples. The DEGs were enriched in extracellular matrix (ECM)-receptor interaction, as well as focal adhesion and transcriptional mis-regulation in cancer. The 2 most crucial regulatory pathways in esophageal cancer were the amebiasis pathway and the PI3K-Akt signaling pathway. Secreted phosphoprotein 1 (SPP1) and fibronectin 1 (FN1) were selected and verified in an independent cohort and samples using the TCGA and GTEx projects. Gene set enrichment analysis (GSEA) showed that proteasome and nucleotide excision repair were 2 most differentially enriched pathways in the SPP1 high-expression phenotype, and ECM-receptor interaction and focal adhesion in FN1 high-expression phenotype. Kaplan-Meier survival analysis showed that SPP1 and FN1 were significantly positively related to overall survival and had the potential to predict patient relapse. Conclusions Our analysis is the first to show that SPP1 and FN1 might work as biological markers of progression and prognosis in esophageal carcinoma (ESCA).
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Affiliation(s)
- Menglu Li
- Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China (mainland)
| | - Kaige Wang
- Department of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China (mainland)
| | - Yanhua Pang
- Department of Gastroenterology, Beijing Chaoyang Hospital, Beijing, China (mainland)
| | - Hongpan Zhang
- Department of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China (mainland)
| | - Hao Peng
- Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China (mainland)
| | - Qi Shi
- Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China (mainland)
| | - Zhiyu Zhang
- Department of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China (mainland)
| | - Xiaobin Cui
- Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China (mainland)
| | - Feng Li
- Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China (mainland).,Department of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China (mainland)
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Xu YW, Chen H, Hong CQ, Chu LY, Yang SH, Huang LS, Guo H, Chen LY, Liu CT, Huang XY, Lin LH, Chen SL, Wu ZY, Peng YH, Xu LY, Li EM. Serum IGFBP-1 as a potential biomarker for diagnosis of early-stage upper gastrointestinal tumour. EBioMedicine 2020; 51:102566. [PMID: 31901863 PMCID: PMC6956950 DOI: 10.1016/j.ebiom.2019.11.027] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 11/15/2019] [Accepted: 11/18/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Early detection would improve upper gastrointestinal cancer prognosis. We aimed to identify serum protein biomarker for the detection of early-stage upper gastrointestinal cancer. METHODS We performed a three-tiered study including 2028 participants from three medical centres. First, we applied two different antibody arrays to screen candidate serum proteins that increased in 20 patients with oesophageal squamous cell carcinoma (ESCC) compared with 20 normal controls. We then evaluated the selected protein by enzyme-linked immunosorbent assay in 1064 participants including 731 upper gastrointestinal cancer patients (287 ESCCs, 237 oesophagogastric junction adenocarcinomas (EJAs), and 207 stomach cancers) and 333 normal controls. The diagnostic value of the selected protein was finally validated in two independent cohorts of ESCC patients and controls (n=472 and 452, respectively). The receiver operating characteristic was used to calculate diagnostic accuracy. FINDINGS Serum insulin-like growth factor binding protein-1 (IGFBP-1) identified in both antibody arrays showed significantly elevated levels in upper gastrointestinal cancers, compared with normal controls. Serum IGFBP-1 provided high diagnostic accuracy of early-stage ESCC, EJA, stomach and cancer (areas under the curve: 0·898, 0·936 and 0·864, respectively). This protein maintained diagnostic performance for early-stage ESCC in independent cohorts 1 and 2 (0·849 and 0·911, respectively). Additionally, serum levels of IGFBP-1 dropped significantly after surgical resection of primary tumours, compared with the corresponding pre-operative ESCC samples (p < 0·05). INTERPRETATION Serum IGFBP-1 represents a promising diagnostic biomarker to detect early-stage upper gastrointestinal cancer.
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Affiliation(s)
- Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China; Precision Medicine Research Centre, Shantou University Medical College, Shantou, China; Guangdong Oesophageal Cancer Research Institute, Shantou University Medical College, Shantou, China
| | - Hao Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Centre, Guangzhou, China
| | - Chao-Qun Hong
- Department of Oncological Laboratory Research, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Ling-Yu Chu
- Precision Medicine Research Centre, Shantou University Medical College, Shantou, China
| | - Shi-Han Yang
- Department of Dermatology and Venereology, Shantou Central Hospital, Shantou, China
| | - Li-Sheng Huang
- Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Hong Guo
- Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Liu-Yi Chen
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China; Precision Medicine Research Centre, Shantou University Medical College, Shantou, China
| | - Xin-Yi Huang
- Precision Medicine Research Centre, Shantou University Medical College, Shantou, China
| | - Lie-Hao Lin
- Department of surgery, Shantou Nan'ao People's Hospital, Shantou, China
| | - Shu-Lin Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Centre, Guangzhou, China
| | - Zhi-Yong Wu
- Department of Surgical Oncology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China.
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China; Precision Medicine Research Centre, Shantou University Medical College, Shantou, China; Guangdong Oesophageal Cancer Research Institute, Shantou University Medical College, Shantou, China.
| | - Li-Yan Xu
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou, China.
| | - En-Min Li
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China.
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Wang Z, Tian X, Sun D, Cao P, Ding M, Li Y, Guo N, Ouyang R, Miao Y. A new Bi2MoO6 nano-tremella-based electrochemical immunosensor for the sensitive detection of a carcinoembryonic antigen. RSC Adv 2020; 10:15870-15880. [PMID: 35493654 PMCID: PMC9052421 DOI: 10.1039/d0ra01922d] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 04/02/2020] [Indexed: 12/31/2022] Open
Abstract
Novel Bi2MoO6 nanohybrids with a tremella-like structure modified with gold nanoparticles were used to fabricate an electrochemical immunosensing platform of CEA.
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Affiliation(s)
- Zhongmin Wang
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Xinli Tian
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Dong Sun
- School of Chemistry and Chemical Engineering
- Henan Normal University
- Xinxiang 453007
- China
| | - Penghui Cao
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Mengkui Ding
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Yuhao Li
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Ning Guo
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Ruizhuo Ouyang
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
| | - Yuqing Miao
- Institute of Bismuth Science
- The University of Shanghai for Science and Technology
- Shanghai 200093
- China
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42
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Qin Y, Wu CW, Taylor WR, Sawas T, Burger KN, Mahoney DW, Sun Z, Yab TC, Lidgard GP, Allawi HT, Buttar NS, Smyrk TC, Iyer PG, Katzka DA, Ahlquist DA, Kisiel JB. Discovery, Validation, and Application of Novel Methylated DNA Markers for Detection of Esophageal Cancer in Plasma. Clin Cancer Res 2019; 25:7396-7404. [PMID: 31527170 PMCID: PMC6911634 DOI: 10.1158/1078-0432.ccr-19-0740] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 06/20/2019] [Accepted: 09/11/2019] [Indexed: 12/29/2022]
Abstract
PURPOSE The burden of esophageal cancer continues to rise, and noninvasive screening tools are needed. Methylated DNA markers (MDM) assayed from plasma show promise in detection of other cancers. For esophageal cancer detection, we aimed to discover and validate MDMs in tissue, and determine their feasibility when assayed from plasma. EXPERIMENTAL DESIGN Whole-methylome sequencing was performed on DNA extracted from 37 tissues (28 EC; 9 normal esophagus) and 8 buffy coat samples. Top MDMs were validated by methylation specific PCR on tissue from 76 EC (41 adeno, 35 squamous cell) and 17 normal esophagus. Quantitative allele-specific real-time target and signal amplification was used to assay MDMs in plasma from 183 patients (85 EC, 98 controls). Recursive partitioning (rPART) identified MDM combinations predictive of esophageal cancer. Validation was performed in silico by bootstrapping. RESULTS From discovery, 23 candidate MDMs were selected for independent tissue validation; median area under the receiver operating curve (AUC) for individual MDMs was 0.93. Among 12 MDMs advanced to plasma testing, rPART modeling selected a 5 MDM panel (FER1L4, ZNF671, ST8SIA1, TBX15, ARHGEF4) which achieved an AUC of 0.93 (95% CI, 0.89-0.96) on best-fit and 0.81 (95% CI, 0.75-0.88) on cross-validation. At 91% specificity, the panel detected 74% of esophageal cancer overall, and 43%, 64%, 77%, and 92% of stages I, II, III, and IV, respectively. Discrimination was not affected by age, sex, smoking, or body mass index. CONCLUSIONS Novel MDMs assayed from plasma detect esophageal cancer with moderate accuracy. Further optimization and clinical testing are warranted.
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Affiliation(s)
- Yi Qin
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Chung W Wu
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - William R Taylor
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Tarek Sawas
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Kelli N Burger
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Douglas W Mahoney
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Zhifu Sun
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Tracy C Yab
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Navtej S Buttar
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Thomas C Smyrk
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Prasad G Iyer
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David A Katzka
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David A Ahlquist
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John B Kisiel
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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43
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Qiu C, Wang P, Wang B, Shi J, Wang X, Li T, Qin J, Dai L, Ye H, Zhang J. Establishment and validation of an immunodiagnostic model for prediction of breast cancer. Oncoimmunology 2019; 9:1682382. [PMID: 32002291 PMCID: PMC6959442 DOI: 10.1080/2162402x.2019.1682382] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 09/25/2019] [Accepted: 10/14/2019] [Indexed: 02/07/2023] Open
Abstract
Serum autoantibodies that react with tumor-associated antigens (TAAs) can be used as potential biomarkers for diagnosis of cancer. This study aims to evaluate the immunodiagnostic value of 11 anti-TAAs autoantibodies for detection of breast cancer (BC) and establish a diagnostic model for distinguishing BC from normal human controls (NHC) and benign breast diseases (BBD). Sera from 10 BC patients and 10 NHC were used to detect 11 anti-TAAs autoantibodies by western blotting. The 11 anti-TAAs autoantibodies were further assessed in 983 sera by relative quantitative enzyme-linked immunosorbent assay (ELISA). Binary logistic regression and Fisher linear discriminant analysis were conducted to establish a prediction model by using 184 BC and 184 NHC (training cohort, n = 568) and validated by leave-one-out cross-validation. Logistic regression model was selected to establish the prediction model. Results were validated using an independent validation cohort (n = 415). The five anti-TAAs (p53, cyclinB1, p16, p62, 14-3-3ξ) autoantibodies were selected to construct the model with the area under the curve (AUC) of 0.943 (95% CI, 0.919–0.967) in training cohort and 0.916 (95% CI, 0.886–0.947) in the validation cohort. In the identification of BC and BBD, AUCs were 0.881 (95% CI, 0.848–0.914) and 0.849 (95% CI, 0.803–0.894) in training and validation cohort, respectively. In summary, our study indicates that the immunodiagnostic model can distinguish BC from NHC and BC from BBD and this model may have a potential application in immunodiagnosis of breast cancer.
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Affiliation(s)
- Cuipeng Qiu
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.,College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China
| | - Peng Wang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.,College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China
| | - Bofei Wang
- College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China
| | - Jianxiang Shi
- College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China.,Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Xiao Wang
- College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China.,Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Tiandong Li
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.,College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China
| | - Jiejie Qin
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.,College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China
| | - Liping Dai
- College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China.,Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Hua Ye
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.,College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China
| | - Jianying Zhang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.,College of Public Health, Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China.,Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
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44
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Xu YW, Peng YH, Xu LY, Xie JJ, Li EM. Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma. World J Gastroenterol 2019; 25:5049-5068. [PMID: 31558856 PMCID: PMC6747294 DOI: 10.3748/wjg.v25.i34.5049] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/28/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EGJA) are the two main types of gastrointestinal cancers that pose a huge threat to human health. ESCC remains one of the most common malignant diseases around the world. In contrast to the decreasing prevalence of ESCC, the incidence of EGJA is rising rapidly. Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers. Current approaches for early diagnosis mainly depend on invasive and costly endoscopy. Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients. Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis, making them promising biomarkers for early detection and monitoring of ESCC and EGJA. In this review, we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.
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Affiliation(s)
- Yi-Wei Xu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Li-Yan Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jian-Jun Xie
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong Province, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
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45
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Xu L, Lee JR, Hao S, Ling XB, Brooks JD, Wang SX, Gambhir SS. Improved detection of prostate cancer using a magneto-nanosensor assay for serum circulating autoantibodies. PLoS One 2019; 14:e0221051. [PMID: 31404106 PMCID: PMC6690541 DOI: 10.1371/journal.pone.0221051] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 07/29/2019] [Indexed: 12/22/2022] Open
Abstract
Purpose To develop a magneto-nanosensor (MNS) based multiplex assay to measure protein and autoantibody biomarkers from human serum for prostate cancer (CaP) diagnosis. Materials and methods A 4-panel MNS autoantibody assay and a MNS protein assay were developed and optimized in our labs. Using these assays, serum concentration of six biomarkers including prostate-specific antigen (PSA) protein, free/total PSA ratio, as well as four autoantibodies against Parkinson disease 7 (PARK7), TAR DNA-binding protein 43 (TARDBP), Talin 1 (TLN1), and Caldesmon 1 (CALD1) and were analyzed. Human serum samples from 99 patients (50 with non-cancer and 49 with clinically localized CaP) were evaluated. Results The MNS assay showed excellent performance characteristics and no cross-reactivity. All autoantibody assays showed a statistically significant difference between CaP and non-cancer samples except for PARK7. The most significant difference was the combination of the four autoantibodies as a panel in addition to the free/total PSA ratio. This combination had the highest area under the curve (AUC)– 0.916 in ROC analysis. Conclusions Our results suggest that this autoantibody panel along with PSA and free PSA have potential to segregate patients without cancer from those with prostate cancer with higher sensitivity and specificity than PSA alone.
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Affiliation(s)
- Lingyun Xu
- Department of Radiology, Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Stanford, California, United States of America
| | - Jung-Rok Lee
- Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul, South Korea
| | - Shiying Hao
- Clinical and Translational Research Program, Betty Irene Moore Children's Heart Center, Lucile Packard Children’s Hospital, Palo Alto, California, United States of America
- Departments of Surgery, Stanford University, Stanford, California, United States of America
| | - Xuefeng Bruce Ling
- Clinical and Translational Research Program, Betty Irene Moore Children's Heart Center, Lucile Packard Children’s Hospital, Palo Alto, California, United States of America
- Departments of Surgery, Stanford University, Stanford, California, United States of America
| | - James D. Brooks
- Department of Urology, Stanford University School of Medicine, Stanford, California, United States of America
| | - Shan X. Wang
- Department of Materials Science & Engineering, Stanford University, Stanford, California, United States of America
- Department of Electrical Engineering, Stanford University, Stanford, California, United States of America
- Department of Radiology, Stanford University School of Medicine, Stanford, California, United States of America
| | - Sanjiv Sam Gambhir
- Department of Radiology, Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Stanford, California, United States of America
- Department of Electrical Engineering, Stanford University, Stanford, California, United States of America
- Department of Bioengineering, Stanford University, Stanford, California, United States of America
- * E-mail:
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46
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Pan J, Zheng QZ, Li Y, Yu LL, Wu QW, Zheng JY, Pan XJ, Xie BS, Wu YA, Qian J, Zhu H, Huang Y. Discovery and Validation of a Serologic Autoantibody Panel for Early Diagnosis of Esophageal Squamous Cell Carcinoma. Cancer Epidemiol Biomarkers Prev 2019; 28:1454-1460. [PMID: 31239266 DOI: 10.1158/1055-9965.epi-18-1269] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 02/14/2019] [Accepted: 06/21/2019] [Indexed: 11/16/2022] Open
Affiliation(s)
- Jianbo Pan
- Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Qing-Zhu Zheng
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China
| | - Yadong Li
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China
| | - Li-Li Yu
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China
| | - Qing-Wei Wu
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China
| | - Jia-Ying Zheng
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China
| | - Xiao-Jie Pan
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Bao-Song Xie
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Respiratory Medicine, Fujian Provincial Hospital, Fuzhou, China
| | - Yan-An Wu
- Provincial Clinical College, Fujian Medical University, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China
| | - Jiang Qian
- Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland.
| | - Heng Zhu
- Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland.
| | - Yi Huang
- Provincial Clinical College, Fujian Medical University, Fuzhou, China.
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China
- Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, China
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47
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Huang X, Hong C, Peng Y, Yang S, Huang L, Liu C, Chen L, Chu L, Xu L, Xu Y. The Diagnostic Value of Serum IGFBP7 in Patients with Esophageal Squamous Cell Carcinoma. J Cancer 2019; 10:2687-2693. [PMID: 31258777 PMCID: PMC6584926 DOI: 10.7150/jca.32393] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 05/01/2019] [Indexed: 02/05/2023] Open
Abstract
Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancer in the world and especially in China with high incidence and mortality. The exploration of novel serum biomarkers is required for early detection of ESCC. We investigated the diagnostic value of serum insulin like growth factor binding protein 7 (IGFBP7) in ESCC, evaluating its potential to improve the diagnosis of ESCC. The serum samples of 106 patients with ESCC and 107 normal controls were tested by enzyme-linked immunosorbent assay (ELISA). The levels of IGFBP7 in ESCC group were significantly higher than that in normal controls, compared by the Mann-Whitney U test (P<0.0001). Using receiver operating characteristic (ROC) curve, the diagnostic value of serum IGFBP7 was demonstrated. Versus normal group, the area under the ROC curve (AUC) of all ESCC was 0.794 (95%CI: 0.735-0.853) and early-stage ESCC was 0.725 (95%CI: 0.633-0.817). With optimized cutoff value of 2.993 ng/mL, IGFBP7 showed certain diagnostic value with specificity of 90.7%, sensitivities of 40.6% and 32.4% in ESCC and early-stage ESCC, respectively. Considering the correlation between clinical data and IGFBP7, no significant association was found (all P>0.05). Thus, we supposed that serum IGFBP7 might be a potential biomarker in the diagnosis of ESCC.
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Affiliation(s)
- Xinyi Huang
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041
| | - Chaoqun Hong
- Department of Oncological Laboratory Research, the Cancer Hospital of Shantou University Medical College, Shantou 515041
| | - Yuhui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou 515041
| | - Shihan Yang
- Department of Dermatology and Venereology, Shantou Central Hospital, Shantou 515041
| | - Lisheng Huang
- Department of Radiation Oncology, the Cancer Hospital of Shantou University Medical College, Shantou 515041
| | - Cantong Liu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041
| | - Liuyi Chen
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041
| | - Lingyu Chu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041
| | - Liyan Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou 515041
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China
| | - Yiwei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou 515041
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou 515041
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48
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Etiology, cancer stem cells and potential diagnostic biomarkers for esophageal cancer. Cancer Lett 2019; 458:21-28. [PMID: 31125642 DOI: 10.1016/j.canlet.2019.05.018] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 04/10/2019] [Accepted: 05/15/2019] [Indexed: 12/19/2022]
Abstract
Esophageal cancer (EC) has been a leading cause of cancer death worldwide in part due to late detection and lack of precision treatment. EC includes two major malignancies, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Recent studies reveal that ESCC and EAC have distinct cell of origin and contain cancer stem cells (also known as tumor initiating cells) expressing different cell surface markers. These biomarkers have potentially important values for both early detection and finding effective therapy. In this review we summarize the updated findings for cell of origin and provide an overview of cancer cell biomarkers that have been tested for ESCC and EAC. In addition, we also discuss recent progress in the study of molecular mechanisms leading to these malignancies.
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49
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Xu YW, Chen H, Guo HP, Yang SH, Luo YH, Liu CT, Huang XY, Tang XM, Hong CQ, Li EM, Xu LY, Peng YH. Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma. Gastric Cancer 2019; 22:546-557. [PMID: 30426295 PMCID: PMC6476828 DOI: 10.1007/s10120-018-0894-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 10/25/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients. METHODS Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. RESULTS We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively). CONCLUSIONS Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.
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Affiliation(s)
- Yi-Wei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, 515041, People's Republic of China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - Hao Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Hai-Peng Guo
- Department of Head and Neck Surgery, The Cancer Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - Shi-Han Yang
- Department of Dermatology and Venereology, Shantou Central Hospital, Shantou, 515041, People's Republic of China
| | - Yu-Hao Luo
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - Xin-Yi Huang
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - Xue-Miao Tang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Chao-Qun Hong
- Department of Oncological Laboratory Research, The Cancer Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - En-Min Li
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, 515041, People's Republic of China.
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, People's Republic of China.
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, People's Republic of China.
| | - Li-Yan Xu
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, 515041, People's Republic of China.
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, People's Republic of China.
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou, 515041, People's Republic of China.
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China.
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, 515041, People's Republic of China.
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, 515041, People's Republic of China.
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Xu YW, Hong CQ, Wu ZY, Peng YH, Ran LQ, Yang SH, Huang BS, Liang XY, Chen HL, Wu JY, Xu XE, Deng JW, Zou HY, Fang WK, Li EM, Xu LY, Xie JJ. Diagnostic and prognostic value of serum L1-cell adhesion molecule in esophageal squamous cell carcinoma. Clin Res Hepatol Gastroenterol 2018; 42:597-603. [PMID: 30219694 DOI: 10.1016/j.clinre.2018.08.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 06/12/2018] [Accepted: 08/15/2018] [Indexed: 02/05/2023]
Abstract
OBJECTIVE L1 cell adhesion molecule (L1CAM) has been found to be dysregulated in several types of human cancers. Here, we aimed to determine the level of soluble L1CAM in serum of patients with esophageal squamous cell carcinoma (ESCC). METHODS Serum levels of L1CAM were determined by an enzyme-linked immunosorbent assay (ELISA) in 191 patients with ESCC and 94 normal controls. Receiver operating characteristics (ROC) was employed to calculate diagnostic accuracy. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the logrank test. RESULTS Levels of L1CAM were significantly lower in all ESCC patients than in normal controls (P < 0.001). Detection of serum L1CAM provided a sensitivity of 28.3%, a specificity of 90.4% and an area under the curve (AUC) of 0.644 (95% CI: 0.579-0.710) in diagnosing ESCC. Similar results were observed in the diagnosis of early-stage ESCC (26.2% sensitivity, 90.4% specificity, and an AUC of 0.629). Moreover, decreased level of L1CAM was correlated with depth of tumor invasion (P < 0.05). Kaplan-Meier analysis showed that lower serum L1CAM level was significantly related to shorter overall survival time (P = 0.036) and disease-free survival time (P = 0.021) of ESCC patients. CONCLUSIONS Our study demonstrated that serum L1CAM might serve as a potential biomarker for the diagnosis and prognosis of ESCC.
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Affiliation(s)
- Yi-Wei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Chao-Qun Hong
- Cancer Research Lab, The Cancer Hospital of Shantou University Medical College, Shantou 515041, PR China
| | - Zhi-Yong Wu
- Department of Surgical Oncology, Shantou Central Hospital, Shantou 515041, PR China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou 515041, PR China
| | - Li-Qiang Ran
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Shi-Han Yang
- Department of Dermatology and Venereology, Shantou Central Hospital, Shantou 515041, PR China
| | - Bin-Sen Huang
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Xiao-Ying Liang
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Hai-Lu Chen
- Department of Surgical Oncology, Shantou Central Hospital, Shantou 515041, PR China
| | - Jian-Yi Wu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Xiu-E Xu
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, PR China
| | - Jian-Wen Deng
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Hai-Ying Zou
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Wang-Kai Fang
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - En-Min Li
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China
| | - Li-Yan Xu
- Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, PR China.
| | - Jian-Jun Xie
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling road, Shantou 515041, PR China.
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