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Sato R, Oikawa M, Kakita T, Abe T, Akazawa N, Okano H, Ito K, Tsuchiya T. Prognostic value of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with obstructive colorectal cancer treated with a self-expandable metallic stent and curative surgery. Surg Today 2025; 55:618-626. [PMID: 39404850 DOI: 10.1007/s00595-024-02943-6] [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: 06/22/2024] [Accepted: 09/02/2024] [Indexed: 04/22/2025]
Abstract
PURPOSE The importance of tumor markers is well established; yet little is known about their prognostic value for patients with obstructive colorectal cancer (OCRC). We investigated the clinical significance of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with non-metastatic OCRC, who underwent insertion of a self-expandable metallic stent and curative surgery. METHODS Clinical data on 91 patients with OCRC were analyzed retrospectively to evaluate the associations of preoperative serum values of tumor makers with short- and long-term outcomes. RESULTS The 91 patients comprised 53 men and 38 women, with a median age of 71 years. Twelve patients had an elevated preoperative CA 19-9 level. Multivariate analyses revealed that an elevated CA 19-9 level was independently associated with poor disease-free survival (DFS) [hazard ratio (HR) = 4.57, 95% confidence interval (CI) 2.06-10.14, P < 0.001] and overall survival (HR = 4.06, 95% CI 1.46-11.24, P = 0.007). A CEA level > 5 ng/ml had no prognostic value, whereas a CEA level > 10.8 ng/ml was significantly associated with worse DFS (P = 0.032). CONCLUSION Measuring the CA 19-9 level concomitantly with the CEA level for patients with advanced CRC, including OCRC, may provide a valuable means to improve prognostication.
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Affiliation(s)
- Ryuichiro Sato
- Departments of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan.
- Department of Surgery, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi, 981-1293, Japan.
| | - Masaya Oikawa
- Departments of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan
| | - Tetsuya Kakita
- Departments of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan
| | - Tomoya Abe
- Departments of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan
| | - Naoya Akazawa
- Departments of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan
| | - Haruka Okano
- Departments of Gastroenterology, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan
| | - Kei Ito
- Departments of Gastroenterology, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan
| | - Takashi Tsuchiya
- Departments of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, 983-0824, Japan
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Li M, Yuan DH, Yang Z, Lu TX, Zhang L. Retrospective analysis of preoperative tumor marker levels in rectal cancer patients: Implications for diagnosis. World J Gastrointest Surg 2025; 17:100820. [PMID: 40162391 PMCID: PMC11948132 DOI: 10.4240/wjgs.v17.i3.100820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 01/20/2025] [Accepted: 02/07/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Early detection of rectal cancer poses significant challenges. Current diagnostic methods, including colonoscopy, imaging techniques, and fecal tests, have limitations such as invasiveness, cost, and varying sensitivity. This study evaluated the diagnostic value of preoperative serum tumor markers in rectal cancer patients. AIM To investigate the value of a multi-marker approach for the preoperative diagnosis of rectal cancer. METHODS A retrospective analysis of 250 patients diagnosed with rectal cancer between July 2022 and July 2024 was conducted. Preoperative alpha-fetoprotein levels, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), CA19-9, CA15-3, and CA72-4 were analyzed. All blood samples were collected under standardized conditions, including fasting status and proper storage methods, within two weeks before surgery. Diagnostic performance was assessed using receiver operating characteristic curve analysis. Correlations among clinicopathological features were also evaluated. RESULTS CEA demonstrated the highest diagnostic performance among individual tumor markers with an area under the curve (AUC) of 0.78 [95% confidence interval (CI): 0.73-0.83]. However, a combination of CEA, CA19-9, and CA72-4 showed superior performance, achieving an AUC of 0.87 (95%CI: 0.83-0.91). Significant correlations were observed between CEA levels and several clinicopathological features, including tumor stage (P < 0.001), lymph node involvement (P = 0.002), and distant metastasis (P < 0.001). Furthermore, in a subgroup analysis of patients diagnosed after July 2022, the integration of fecal occult blood testing with the tumor marker panel (CEA + CA19-9 + CA72-4) significantly improved diagnostic accuracy, increasing the AUC to 0.91 (95%CI: 0.86-0.96). CONCLUSION A multimarker approach combining CEA, CA19-9, and CA72-4 with fecal occult blood testing enhances the preoperative assessment of patients with rectal cancer. These findings suggest potential improvements in risk stratification and management of patients with rectal cancer.
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Affiliation(s)
- Ming Li
- Clinical Laboratory, Linquan County People’s Hospital, Linquan 236400, Anhui Province, China
| | - Da-Hao Yuan
- Clinical Laboratory, Linquan County People’s Hospital, Linquan 236400, Anhui Province, China
| | - Zhi Yang
- Clinical Laboratory, Linquan County People’s Hospital, Linquan 236400, Anhui Province, China
| | - Teng-Xiang Lu
- Hemodialysis Center, Linquan County People’s Hospital, Linquan 236400, Anhui Province, China
| | - Lei Zhang
- Department of Gastrointestinal Surgery, Linquan County People’s Hospital, Linquan 236400, Anhui Province, China
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Ye QY, Wang YY, Wang ZJ, Lu M, Peng HX, Wang X, Cheng XX, Ying HQ. Robust Predictive Performance of MLPAS and CCMLP for Clinical Outcome and Risk Stratification in Patients with Colorectal Cancer. J Inflamm Res 2025; 18:3889-3900. [PMID: 40109656 PMCID: PMC11921802 DOI: 10.2147/jir.s498028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 02/10/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND There is no recognized biomarker is recommended to monitor or predict the prognosis of colorectal cancer (CRC) patients with negative detection of carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) and to classify high recurrence-risk cases. METHODS Discovery and two-stage validation cohorts, which included 2111 radically resected patients with stage II-III CRC, were enrolled in this study. We detected preoperative peripheral monocyte, platelet, albumin (Alb), pre-albumin (pAlb), CEA, and CA19-9 and investigated the prognostic and risk-stratified roles of twelve new inflammatory biomarkers in the three cohorts. RESULTS In our study, monocyte-to-pAlb ratio (MPAR), monocyte-to-lymphocyte -to-Alb ratio (MLAR), monocyte-to-lymphocyte-to-pAlb ratio (MLPAR), monocyte- to-pAlb score (MPAS), lymphocyte-to-monocyte-Alb score (MLAS), lymphocyte-to monocyte-pAlb score (MLPAS), and platelet-to-lymphocyte-Alb score (PLAS) were significantly associated with both RFS and OS in three cohorts. MLPAS showed the best performance in predicting RFS and OS, and it was related to right-tumor location and significant cancer burden (≥5cm) in the overall population. Moreover, MLPAS is a robust prognostic biomarker in subgroups stratified by CEA or CA19-9. Patients with scores zero and two of the CEA-CA19-9-MLPAS score (CCMLP) showed the lowest and highest recurrence and death rates, respectively, and significant survival differences were observed between them. CONCLUSION MLPAS is an optimal, independent, and robust prognostic biomarker in the stage II-III CRC population, especially with negative CEA or CA19-9. The CCMLP could effectively classify high recurrence-risk patients who require more focus, monitoring, and treatment for the clinic.
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Affiliation(s)
- Qiu-Ying Ye
- Department of Clinical Laboratory, Immunity and Inflammation Key Laboratory of Jiangxi Province, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
- Department of Medical Technology, Jiangxi Medical College, Shangrao, 334000, People’s Republic of China
- Department of Laboratory Medicine, Central Hospital of Shangrao City, Shangrao, 334000, People’s Republic of China
| | - Yuan-Yuan Wang
- Department of Clinical Laboratory, Immunity and Inflammation Key Laboratory of Jiangxi Province, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
| | - Zhi-Jie Wang
- Department of Clinical Laboratory, Immunity and Inflammation Key Laboratory of Jiangxi Province, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
| | - Min Lu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
| | - Hong-Xin Peng
- Department of Clinical Laboratory, Nanjing First Hospital, Nanjing, 210006, People’s Republic of China
| | - Xin Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, People’s Republic of China
| | - Xue-Xin Cheng
- Department of Clinical Laboratory, Immunity and Inflammation Key Laboratory of Jiangxi Province, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
| | - Hou-Qun Ying
- Department of Clinical Laboratory, Immunity and Inflammation Key Laboratory of Jiangxi Province, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China
- Department of Laboratory Medicine, Central Hospital of Shangrao City, Shangrao, 334000, People’s Republic of China
- Shangrao Medical Center, The Second Affiliated Hospital of Nanchang University, Shangrao, 334000, People’s Republic of China
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Ge H, Cai R, Chen X, Liu B, Hu X, Deng S, Li H, Dai L, Tang J, Tang H, Gong X, Wu C, Wang G, Li G, Liu B, Wang J, Tang Y, Li X, Feng J. Clinical Relevance of Elevated Serum Carcinoembryonic Antigen in Allergic Bronchopulmonary Aspergillosis/Mycosis: A Multicenter Retrospective Study. J Asthma Allergy 2024; 17:1313-1323. [PMID: 39737334 PMCID: PMC11683200 DOI: 10.2147/jaa.s494250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 12/17/2024] [Indexed: 01/01/2025] Open
Abstract
Background Allergic bronchopulmonary aspergillosis/mycosis (ABPA/M) is a complex non-infectious pulmonary benign disease characterized by an immune response against aspergillus/fungus. Carcinoembryonic antigen (CEA), typically recognized as a tumor marker, also elevated in certain benign diseases. Few studies on ABPA/M cases presenting with elevated serum CEA levels have been reported. Patients and Methods A cohort of 115 patients diagnosed as ABPA/M were divided into two groups (CEA normal and CEA elevated). The characteristics of ABPA/M patients in terms of its demographic profile, clinical symptoms, pertinent clinical laboratory examinations were analyzed. Levels of cytokines (IL-4, IL-5, GM-CSF, IFN-γ) were analyzed by enzyme-linked immunosorbent assay. Comparative evaluation included pre-therapy and post-treatment eosinophil count and total IgE level, to evaluate therapeutic disparities between the two groups. Results Among 115 cases of ABPA/M, 32 exhibited elevated serum CEA levels above baseline and 83 were normal. ABPA/M patients with elevated serum CEA tended to be younger (50, IQR [43-56] years vs 59, IQR [47-68] years; P < 0.05) with superior pulmonary function (FEV1/FVC ratio, 65.1% (44.2, 79.6) vs 79.1% (65.2, 84.2), P < 0.05), and showed marginally higher baseline levels of the total IgE (P < 0.05), blood eosinophils counts and ratios (P < 0.01) compared to those with normal CEA. Higher serum levels of IL-4, IL-5, GM-CSF and IFN-γ in ABPA/M patients with elevated serum CEA levels were observed (P < 0.0001). After treatment (at 12w), compared to ABPA/M patients with normal serum CEA, the decrease in eosinophil count and total IgE levels was less pronounced in ABPA/M patients with elevated serum CEA eosinophil count, 523±481.66 vs 267±200.68, P < 0.05; total IgE, 619±680.47 vs 263±400.90, P < 0.05), which indicates a poor response to treatment. Conclusion Monitoring serum CEA levels may serve as a supplementary tool in the clinical management of ABPA/M patients.
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Affiliation(s)
- Huan Ge
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Runjin Cai
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Xuemei Chen
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Bin Liu
- Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Xinyue Hu
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Shuanglinzi Deng
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Hui Li
- Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, People’s Republic of China
| | - Lixue Dai
- The Second Department of Respiratory Disease, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China
| | - Jiale Tang
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Huan Tang
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Xiaoxiao Gong
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Chendong Wu
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Guo Wang
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Guotao Li
- Department of Infectious Diseases, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, People’s Republic of China
| | - Bing Liu
- Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China
- Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, People’s Republic of China
| | - Jun Wang
- The Second Department of Respiratory Disease, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China
| | - Yuling Tang
- Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, People’s Republic of China
| | - Xiaozhao Li
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- Department of Nephrology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Juntao Feng
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China
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Ji J, Wang C, Goel A, Melstrom K, Zerhouni Y, Lai L, Melstrom L, Raoof M, Fong Y, Kaiser A, Fakih M. Circulating Tumor DNA Testing in Curatively Resected Colorectal Cancer and Salvage Resection. JAMA Netw Open 2024; 7:e2452661. [PMID: 39729315 PMCID: PMC11681374 DOI: 10.1001/jamanetworkopen.2024.52661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 10/31/2024] [Indexed: 12/28/2024] Open
Abstract
Importance Serial circulating tumor DNA (ctDNA) has emerged as a routine surveillance strategy for patients with resected colorectal cancer, but how serial ctDNA monitoring is associated with potential curative outcomes has not been formally assessed. Objective To examine whether there is a benefit of adding serial ctDNA assays to standard-of-care imaging surveillance for potential curative outcomes in patients with resected colorectal cancer. Design, Setting, and Participants In this single-center (City of Hope Comprehensive Cancer Center, Duarte, California), retrospective, case cohort study, patients with stage II to IV colorectal cancer underwent curative resection and were monitored with serial ctDNA assay and National Cancer Center Network (NCCN)-guided imaging surveillance from September 20, 2019, to April 3, 2024. The median duration of follow-up was 26 months (range, 2-54 months). Interventions Serial ctDNA assays were performed every 3 months for 2 years and every 6 months for the 3 following years in conjunction with NCCN-guided radiographic surveillance. Main Outcomes and Measures The primary outcome was the proportion of patients with clinical benefit from ctDNA testing, defined as the proportion of patients with a newly positive ctDNA assay and negative scheduled imaging (most recent or concurrent) that subsequently led to early imaging confirmation of recurrence, followed by curative-intent intervention with no evidence of recurrence at the time of data cutoff. Recurrence was categorized by ctDNA recurrence, radiographic recurrence, or concurrent ctDNA and imaging recurrence. Salvage resections and associated durable remissions were described within each of the 3 categories. Descriptive statistics were used to characterize the patient population. Results In total, 184 patients (median age, 59 years [range, 32-88 years]; 97 female [52.7%]) were included in this study, and 129 (70.1%) had stage II to III disease. Forty-five patients (24.5%) had ctDNA or imaging-confirmed recurrence. Of these 45 patients, 14 had radiographic recurrence with negative ctDNA, and 11 had concurrent ctDNA and imaging recurrence. Twenty of 45 patients had ctDNA positivity with negative imaging at first ctDNA positivity; 6 had reflex imaging that was positive for recurrence, and 14 continued with serial imaging and ctDNA monitoring. Ten of 14 patients had subsequent recurrent disease, 3 patients had a spontaneous clearance of ctDNA, and 1 patient remained imaging negative 7 months after positive ctDNA, after which she was lost to follow-up. Altogether, 11 of 20 patients with ctDNA recurrence without initial concurrent imaging recurrence had subsequent metastasectomy, and only 3 were disease-free at the cutoff date in April 2024, representing 1.6% of the surveilled population. Conclusions and Relevance In this cohort study of patients with stage II to IV colorectal cancer who underwent curative-intent resection, the addition of serial tumor-informed ctDNA assay to the standard NCCN-recommended surveillance had limited clinical benefits. Additional prospective research is needed to clarify the value of ctDNA testing in the surveillance setting.
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Affiliation(s)
- Jingran Ji
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Chongkai Wang
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Kurt Melstrom
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Yasmin Zerhouni
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Lily Lai
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Laleh Melstrom
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Mustafa Raoof
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Yuman Fong
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Andreas Kaiser
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Marwan Fakih
- Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California
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Woodard GA, Kane ER, Todorovic N, Prince S, Dacic S, Chen L. Sex-based differences in CEACAM5 expression in lung cancer. Transl Cancer Res 2024; 13:6394-6402. [PMID: 39697744 PMCID: PMC11651760 DOI: 10.21037/tcr-24-983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 09/30/2024] [Indexed: 12/20/2024]
Abstract
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is expressed in 20-25% of non-small cell lung cancer (NSCLC) and there is interest in CEACAM5 as a biomarker given its potential for blood-based detection and investigational study as a drug target. Increased expression of CEACAM5 has been observed in semi-solid lung adenocarcinoma lesions, which have an increased prevalence in women and never smokers. Given this association, sex-based differences in CEACAM5 were evaluated. The Cancer Genome Atlas (TCGA) data on CEACAM5 expression in NSCLC tumors (n=994) in women (n=398) and men (n=596) were analyzed for differences in expression of CEACAM5 based on sex and histologic subtypes of adenocarcinoma and for correlations with overall survival (OS). Among all stages of NSCLC, mean expression of CEACAM5 was 143.3 fragments per kilobase of transcript per million (FPKM) with differences observed between female and male patients (194.5 vs. 109.2 FPKM, P<0.0001) and between adenocarcinoma and squamous cell carcinoma (239.3 vs. 46.2 FPKM, P<0.0001). Differences persisted among combined sex and histology subgroups. High CEACAM5 was not predictive of survival in NSCLC or adenocarcinoma overall, but was associated with worse survival among stage I female patients with adenocarcinoma (5-year OS CEACAM5 high =33% vs. low =64%, log-rank P=0.008). Higher levels of CEACAM5 expression are observed in NSCLC tumors in female patients and adenocarcinoma histology. High CEACAM5 expression in lung adenocarcinoma is associated with worse survival among female patients. The biologic impact of sex on CEACAM5 as a biomarker warrants further study.
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Affiliation(s)
| | - Emma R. Kane
- Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Nicholas Todorovic
- Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
| | - Samantha Prince
- Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
| | - Sanja Dacic
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Lieping Chen
- Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
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Xie H, Wei L, Wang Q, Tang S, Gan J. Grading carcinoembryonic antigen levels can enhance the effectiveness of prognostic stratification in patients with colorectal cancer: a single-centre retrospective study. BMJ Open 2024; 14:e084219. [PMID: 39477273 PMCID: PMC11529588 DOI: 10.1136/bmjopen-2024-084219] [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: 01/15/2024] [Accepted: 10/02/2024] [Indexed: 11/03/2024] Open
Abstract
OBJECTIVES This study developed a refined carcinoembryonic antigen (CEA) grading system using CEA cut-off points of 5, 20 and 50 ng/mL and to explore the prognostic value of CEA grading in predicting the progression-free survival (PFS) and overall survival (OS) of colorectal cancer (CRC) patients. DESIGN A retrospective cohort study. SETTING First Affiliated Hospital of Guangxi Medical University. PARTICIPANTS 1107 CRC patients who received surgical treatment. MATERIALS AND METHODS Survival analysis was conducted using the Kaplan-Meier method and compared using the log-rank test. A Cox regression model with a 95% CI was used to evaluate the independent prognostic risk factors for CRC. Prognostic nomograms were constructed to predict the 1-5-year PFS/OS. RESULTS Elevated serum CEA levels are often indicative of recurrence and death in CRC patients. Higher CEA levels were significantly associated with more aggressive tumour phenotypes. The CEA grading system was an independent predictor of prognosis in CRC patients and effectively stratified PFS (62.0% vs 51.2% vs 33.7% vs 20.2%, p<0.001) and OS (64.7% vs 54.4% vs 36.6% vs 22.5%, p<0.001) in CRC patients. As the CEA grade increased, the risk of poor prognosis gradually increased in a gradient manner, with an approximately 10% difference in risk grade between each CEA grade. The internal validation cohort further confirmed that CEA grade remains an effective prognostic factor for the survival of CRC patients. Prognostic nomograms, which integrate individual characteristics, tumour features and CEA grading, provide a more comprehensive prognostic evaluation for CRC patients. CONCLUSIONS The CEA grading system is an independent predictor of prognosis for CRC patients and can effectively stratify PFS and OS.
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Affiliation(s)
- Hailun Xie
- Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Lishuang Wei
- Geriatric respiratory medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Qiwen Wang
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Shuangyi Tang
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jialiang Gan
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Lișcu HD, Verga N, Atasiei DI, Badiu DC, Dumitru AV, Ultimescu F, Pavel C, Stefan RE, Manole DC, Ionescu AI. Biomarkers in Colorectal Cancer: Actual and Future Perspectives. Int J Mol Sci 2024; 25:11535. [PMID: 39519088 PMCID: PMC11546354 DOI: 10.3390/ijms252111535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 10/23/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
Biomarkers in colorectal cancer (CRC) are of great interest in the current literature due to improvements in techniques such as liquid biopsy and next-generation sequencing (NGS). However, screening methods vary globally, with multi-target stool DNA (mt-sDNA) predominantly used in the USA and, more recently, the Cologuard Plus; biomarkers such as the Galectins family and septins show promise in early detection. Gut microbiome assessments, such as Fusobacterium nucleatum, are under intense exploration. Diagnostic tests, such as circulating DNA analysis via NGS, exhibit effectiveness and are being increasingly adopted. Circulating tumor cells emerge as potential alternatives to traditional methods in terms of diagnosis and prognosis. Predictive biomarkers are well established in guidelines; nonetheless, with the aid of machine learning and artificial intelligence, these biomarkers may be improved. This review critically explores the actual dynamic landscape of CRC biomarkers and future, promising biomarkers involved in screening, diagnosis, and prognosis.
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Affiliation(s)
- Horia-Dan Lișcu
- Discipline of Oncological Radiotherapy and Medical Imaging, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (H.-D.L.); (A.-I.I.)
- Radiotherapy Department, Colțea Clinical Hospital, 030167 Bucharest, Romania;
| | - Nicolae Verga
- Radiotherapy Department, Colțea Clinical Hospital, 030167 Bucharest, Romania;
| | - Dimitrie-Ionuț Atasiei
- Discipline of Oncological Radiotherapy and Medical Imaging, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (H.-D.L.); (A.-I.I.)
| | - Dumitru-Cristinel Badiu
- Department of Surgery, Bagdasar Arseni Clinical Emergency Hospital, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Bd., 050474 Bucharest, Romania;
| | - Adrian Vasile Dumitru
- Department of Pathology, University Emergency Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Bd., 050474 Bucharest, Romania;
| | - Flavia Ultimescu
- Department of Pathology, Institute of Oncology Alexandru Trestioreanu, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Christopher Pavel
- Department of Gastroenterology, Floreasca Emergency Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Roxana-Elena Stefan
- General Surgery Department, Clinic of General and Esophageal Surgery, Sf. Maria Clinical Hospital, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Diandra-Carmen Manole
- Department of Endocrinology, Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Bd., 050474 Bucharest, Romania;
| | - Andreea-Iuliana Ionescu
- Discipline of Oncological Radiotherapy and Medical Imaging, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (H.-D.L.); (A.-I.I.)
- Radiotherapy Department, Colțea Clinical Hospital, 030167 Bucharest, Romania;
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9
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Zhen J, Li J, Liao F, Zhang J, Liu C, Xie H, Tan C, Dong W. Development and validation of machine learning models for young-onset colorectal cancer risk stratification. NPJ Precis Oncol 2024; 8:239. [PMID: 39438621 PMCID: PMC11496529 DOI: 10.1038/s41698-024-00719-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024] Open
Abstract
Incidence of young-onset colorectal cancer (YOCRC, younger than 50) has significantly increased worldwide. The performance of fecal immunochemical test in detecting YOCRC is unsatisfactory. Using routine clinical data, we aimed to develop machine learning (ML) models to identify individuals with high-risk YOCRC who require further colonoscopy. We retrospectively extracted data of 10,874 young individuals. Multiple supervised ML techniques were devised to distinguish individuals with and without CRC, classifiers were trained, internally validated and temporally validated. In internal validation cohort, Random Forest (RF) ML model demonstrated good performance with AUC of 0.859 and highest recall of 0.840. In temporal validation cohort, the RF ML model also exhibited good classification performance, achieving AUC of 0.888 and highest recall of 0.872. RF algorithm-based approach is effective and feasible in YOCRC risk stratification. This could be valuable in assessing the risk of YOCRC so that clinical management, including further colonoscopy, can be subsequently made. (Registration: This study was registered with ClinicalTrials.gov (NCT06342622) on March 15, 2024.).
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Affiliation(s)
- Junhai Zhen
- Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Jiao Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Fei Liao
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Jixiang Zhang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Chuan Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Huabing Xie
- Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Cheng Tan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Weiguo Dong
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
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10
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Dai X, Li Y, Wang H, Dai Z, Chen Y, Liu Y, Huang S. Development and validation of nomograms based on pre-/post-operative CEA and CA19-9 for survival predicting in stage I-III colorectal cancer patients after radical resection. Front Oncol 2024; 14:1402847. [PMID: 39464705 PMCID: PMC11502300 DOI: 10.3389/fonc.2024.1402847] [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: 03/18/2024] [Accepted: 09/24/2024] [Indexed: 10/29/2024] Open
Abstract
Background Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels. Methods 1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage. Results The overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage. Conclusion Nomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage.
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Affiliation(s)
- Xuan Dai
- Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yifan Li
- Department of Gastrointestinal Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, China
| | - Haoran Wang
- The First Clinical School, Xinxiang Medical University, Xinxiang, Henan, China
| | - Zhujiang Dai
- Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuanyuan Chen
- Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yun Liu
- Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shiyong Huang
- Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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11
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Wang B, Huang J, Chen L. Management of medullary thyroid cancer based on variation of carcinoembryonic antigen and calcitonin. Front Endocrinol (Lausanne) 2024; 15:1418657. [PMID: 39449744 PMCID: PMC11499115 DOI: 10.3389/fendo.2024.1418657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 09/25/2024] [Indexed: 10/26/2024] Open
Abstract
Carcinoembryonic antigen (CEA) and calcitonin (Ctn) are pivotal biomarkers in the diagnosis and management of medullary thyroid carcinoma (MTC). However, their diagnostic reliability in perioperative period remains a topic of ongoing debate. This review synthesizes researches on perioperative fluctuations in CEA and Ctn levels, and evaluates the impact of their different combinations on MTC diagnosis, treatment decisions, and prognosis. Our findings highlight it is crucial to understand and interpret the various combinations of CEA and Ctn fluctuations within a clinical context. Furthermore, to reduce diagnostic errors and improve patient outcomes, we recommend follow-up diagnostic and treatment protocols designed to address the potential pitfalls associated with the use of these biomarkers.
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Affiliation(s)
- Bo Wang
- Department of Paediatric Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Jie Huang
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Chen
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilian University of Munich, Munich, Germany
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12
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Khan F, Abdulla N, du Plessis TL, Karlsson K, Barrow P, Bebington B, Gu L, Kaur M. Identification and Validation of Biomarkers to Predict Early Diagnosis of Inflammatory Bowel Disease and Its Progression to Colorectal Cancer. Biochem Genet 2024:10.1007/s10528-024-10917-z. [PMID: 39325241 DOI: 10.1007/s10528-024-10917-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/13/2024] [Indexed: 09/27/2024]
Abstract
Inflammatory bowel disease (IBD) has become a common global health problem as prevalence continues to rise. It is often associated with increased risk of colorectal cancer (CRC) development. Limitations in current IBD biomarker-based diagnosis hinder the accuracy of early detection of CRC progression. Therefore, in this study, we proposed the use of transcription factor (TF)-based biomarkers that can potentially detect the transition of IBD to CRC. Various bioinformatic analysis and online database validations, and RT-qPCR validations were performed to identify possible diagnostic TFs. RUNX1 was identified as a promising TF that regulates 106 IBD/CRC-related genes. The incorporation of RUNX1 in combination with currently known IBD biomarkers, FEV + NFKB1 + RELA, achieved a comparable sensitivity and specificity scores of 99% and 87%, respectively, while RUNX1 in combination with known CRC markers, CEA + TIMP1 + CA724 + CA199, achieved a sensitivity and specificity score of 97% and 99%, respectively. Furthermore, a small pilot RT-qPCR-based analysis confirmed a demarcated shift in expression profiles in CA724, CEA, RUNX1 and TIMP1 in IBD patients compared to CRC patients' tissue samples. Specifically, CA724 is noticeably elevated in IBD, while the levels of CEA, RUNX1 with TIMP1 are probable genes that may be employed in discerning IBD progression to CRC. Therefore, these preliminary results once validated in large patient cohorts could potentially have a significant impact on CRC disease stratification, resulting in a more precise prediction for treatment and treatment outcomes, especially in South African patients.
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Affiliation(s)
- Farhat Khan
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Naaziyah Abdulla
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Thea-Leonie du Plessis
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Kay Karlsson
- Wits Donald Gordon Medical Centre, Park Town, Johannesburg, 2193, South Africa
| | - Peter Barrow
- Wits Donald Gordon Medical Centre, Park Town, Johannesburg, 2193, South Africa
| | - Brendan Bebington
- Wits Donald Gordon Medical Centre, Park Town, Johannesburg, 2193, South Africa
| | - Liang Gu
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa
| | - Mandeep Kaur
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Johannesburg, WITS-2050, South Africa.
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13
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Li J, Yao H, Lu Y, Zhang S, Zhang Z. Chinese national clinical practice guidelines on prevention, diagnosis and treatment of early colorectal cancer. Chin Med J (Engl) 2024; 137:2017-2039. [PMID: 39104005 PMCID: PMC11374253 DOI: 10.1097/cm9.0000000000003253] [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: 01/08/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established. METHODS This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. RESULTS This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines. CONCLUSIONS The 46 recommendations in this CPG are formed with consideration for stakeholders' values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.
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Affiliation(s)
- Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
| | - Hongwei Yao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Yun Lu
- Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing 100050, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
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14
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Pu W, Chen F, Tang Y, Qu Y, Han Y, Zha J, Jin J, Kong F. Potential value of detection of minimal residual disease in colorectal cancer following radical resection. Chin J Cancer Res 2024; 36:442-454. [PMID: 39246709 PMCID: PMC11377885 DOI: 10.21147/j.issn.1000-9604.2024.04.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 08/14/2024] [Indexed: 09/10/2024] Open
Abstract
Although there has been significant advancement in the identification and management of colorectal cancer (CRC) in recent years, there is still room for improvement in the current standard treatment regimen. One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care. Due to its dynamic, effective, and non-invasive benefits over tissue biopsy, the detection of minimal or molecular residual lesions (MRD) based on circulating tumor DNA (ctDNA) is beneficial to the clinical development of drugs for patients with CRC after radical treatment, as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution. The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions (upgrade or downgrade treatment) in CRC, stratify the risk of clinical recurrence more precisely, and predict the risk of recurrence in advance of imaging examination, according to a large number of observational or prospective clinical studies. With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA, which also improves the accuracy of clinical recurrence risk assessment for CRC. Therefore, it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized, stratified precision therapy; however, additional confirmation will require subsequent high-quality, prospective, large-scale randomized controlled studies. This article will provide an overview of the definition and clinical significance of MRD, the primary indications and technological challenges for MRD detection, along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.
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Affiliation(s)
- Wenji Pu
- Medical Department of Shenzhen University/General Hospital of Shenzhen University/Academy of Clinical Medicine of Shenzhen University, Shenzhen 518055, China
- Department of Clinical Oncology, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
- Department of Radiotherapy, National Cancer Center/National Cancer Clinical Medical Research Center/Shenzhen Hospital, Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences, Shenzhen 518116, China
| | - Fang Chen
- Department of Clinical Oncology, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Yuan Tang
- Department of Radiotherapy, National Cancer Center/National Cancer Clinical Medical Research Center/Shenzhen Hospital, Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences, Shenzhen 518116, China
| | - Yanling Qu
- Department of Clinical Oncology, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Yunzhu Han
- Department of Clinical Oncology, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Jiandong Zha
- Department of Clinical Oncology, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Jing Jin
- Department of Radiotherapy, National Cancer Center/National Cancer Clinical Medical Research Center/Shenzhen Hospital, Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences, Shenzhen 518116, China
| | - Fengming Kong
- Department of Clinical Oncology, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
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15
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Plage H, Furlano K, Neymeyer J, Weinberger S, Gerdes B, Hubatsch M, Ralla B, Franz A, Fendler A, de Martino M, Roßner F, Schallenberg S, Elezkurtaj S, Kluth M, Lennartz M, Blessin NC, Marx AH, Samtleben H, Fisch M, Rink M, Kaczmarek K, Ecke T, Hallmann S, Koch S, Adamini N, Minner S, Simon R, Sauter G, Weischenfeldt J, Klatte T, Schlomm T, Horst D, Zecha H, Slojewski M. CEA (CEACAM5) expression is common in muscle-invasive urothelial carcinoma of the bladder but unrelated to the disease course. BJUI COMPASS 2024; 5:585-592. [PMID: 38873357 PMCID: PMC11168773 DOI: 10.1002/bco2.354] [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: 12/11/2023] [Accepted: 02/26/2024] [Indexed: 06/15/2024] Open
Abstract
Objectives Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours (p < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival (p > 0.25). Conclusion CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs.
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Affiliation(s)
- Henning Plage
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Kira Furlano
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Jörg Neymeyer
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Sarah Weinberger
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Benedikt Gerdes
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Mandy Hubatsch
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Bernhard Ralla
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Antonia Franz
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Annika Fendler
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Michela de Martino
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Florian Roßner
- Institute of PathologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Simon Schallenberg
- Institute of PathologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Sefer Elezkurtaj
- Institute of PathologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Martina Kluth
- Institute of PathologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Maximilian Lennartz
- Institute of PathologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Niclas C. Blessin
- Institute of PathologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Andreas H. Marx
- Department of PathologyAcademic Hospital FuerthFuerthGermany
| | | | - Margit Fisch
- Department of UrologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Michael Rink
- Department of UrologyMarienhospital HamburgHamburgGermany
| | - Krystian Kaczmarek
- Department of Urology and Urological OncologyPomeranian Medical UniversitySzczecinPoland
| | - Thorsten Ecke
- Department of UrologyHelios Hospital Bad SaarowBad SaarowGermany
| | - Steffen Hallmann
- Department of UrologyHelios Hospital Bad SaarowBad SaarowGermany
| | - Stefan Koch
- Department of PathologyHelios Hospital Bad SaarowBad SaarowGermany
| | - Nico Adamini
- Department of UrologyAlbertinen HospitalHamburgGermany
| | - Sarah Minner
- Institute of PathologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Ronald Simon
- Institute of PathologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Guido Sauter
- Institute of PathologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Joachim Weischenfeldt
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
- Biotech Research & Innovation Center (BRIC)University of CopenhagenCopenhagenDenmark
- Finsen LaboratoryRigshospitaletCopenhagenDenmark
| | - Tobias Klatte
- Department of UrologyHelios Hospital Bad SaarowBad SaarowGermany
| | - Thorsten Schlomm
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - David Horst
- Institute of PathologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Henrik Zecha
- Department of UrologyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of HealthBerlinGermany
- Department of UrologyAlbertinen HospitalHamburgGermany
| | - Marcin Slojewski
- Department of Urology and Urological OncologyPomeranian Medical UniversitySzczecinPoland
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Wang J, Song Z. Analysis of risk factors for postoperative recurrence of stage I colorectal cancer: a retrospective analysis of a large population. Front Surg 2024; 11:1388250. [PMID: 38712335 PMCID: PMC11072714 DOI: 10.3389/fsurg.2024.1388250] [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: 02/19/2024] [Accepted: 04/08/2024] [Indexed: 05/08/2024] Open
Abstract
Background Colorectal cancer (CRC) is the third most common cancer worldwide. Patients diagnosed with stage I CRC typically do not require postoperative adjuvant treatment. However, postoperative recurrence is present in at least 40% of patients with CRC and often occurs in those with stage I disease. This study aimed to elucidate the current status of recurrence and clinicopathological characteristics in patients with stage I CRC. Methods Data of indicated patients were obtained from 18 registries in Surveillance, Epidemiology, and End Results (SEER). The multivariable Fine-Gray regression model was used to identify the mortality risk of patients. Disparities in survival were analyzed using Kaplan-Meier curves. Logistic regression was employed to identify factors associated with recurrent risk overestimation. Results Our study indicated a recurrence rate of 15.04% (1,874/12,452) in stage I CRC cases. Notably, we identified race, age, T stage, and carcinoembryonic antigen (CEA) levels as independent risk factors for tumor recurrence, substantially impacting prognosis. Furthermore, gender, race (Black), age (>65 years), elevated CEA levels, and refusal or unknown status regarding radiotherapy significantly correlated with an adverse prognosis in patients with stage I CRC. Conclusions We identified certain key clinicopathological features of patients with stage I CRC and demonstrated the survival benefits of radiotherapy, offering a new perspective on stage I CRC follow-up and treatment recommendations.
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Affiliation(s)
- Jiawei Wang
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Biological Treatment of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine Research on Anorectal Diseases of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhangfa Song
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Biological Treatment of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Integrated Traditional Chinese and Western Medicine Research on Anorectal Diseases of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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17
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Tong S, Wu R, Zhang L, Lu P, Hu X, Li Y, Peng J. Association of preoperative and recurrent serum carcinoembryonic antigen and outcome of colorectal cancer patients with metastatic relapse. Heliyon 2024; 10:e29347. [PMID: 38617920 PMCID: PMC11015133 DOI: 10.1016/j.heliyon.2024.e29347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 04/03/2024] [Accepted: 04/05/2024] [Indexed: 04/16/2024] Open
Abstract
Background Seldom have the associations of preoperative CEA (p-CEA) and recurrent CEA (r-CEA) levels as well as changes in p-CEA and r-CEA with survival in patients with stage I-III colorectal cancer (CRC) who have experienced metastatic relapse, been thoroughly examined. Methods 241 consecutive patients with stage I-III CRC who experienced metastatic relapse at Fudan University Shanghai Cancer Center (FUSCC) between January 2008 and January 2016 were investigated. The influence of p-CEA, r-CEA and CEA alteration on the overall survival (OS) and relapse-to-death survival (RDS) was evaluated. The restricted cubic spline regression model was employed to explore the optimal cut-off value of CEA. Results All 241 patients were categorized into four groups built on their CEA alteration patterns as follows: A, patients presenting elevated p-CEA levels but normal r-CEA levels (P-N); B, patients displaying normal levels of both p-CEA and r-CEA (N-N); C, patients exhibiting elevated levels of both p-CEA and r-CEA (P-P); D, patients with normal p-CEA levels but elevated r-CEA levels (N-P). The correlation between p-CEA and OS (P = 0.3266) and RDS (P = 0.2263) was insignificant. However, r-CEA exhibited a significant association with both OS (P = 0.0005) and RDS (P = 0.0002). Group A demonstrated the longest OS and RDS, whereas group D exhibited the poorest OS and RDS outcomes. For both OS and RDS, the CEA alteration groups served as an independent prognostic indicator. The optimal cut-off threshold for CEA was determined to be 5.1 ng/ml via the restricted cubic spline regression model. Conclusion r-CEA has a stronger correlation with OS and RDS in individuals with stage I-III CRC who have experienced metastatic relapse.The change between p-CEA and r-CEA could further indicate post-relapse survival, thereby facilitating the assessment of mortality risk stratification in stage I-III CRC patients experiencing metastatic relapse.
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Affiliation(s)
- Shanyou Tong
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Renping Wu
- Clinical College of Xiangnan University, Chenzhou, 423000, China
| | - Long Zhang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Ping Lu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xiang Hu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yaqi Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Junjie Peng
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
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18
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Guo N, Zhou Q, Chen X, Zeng B, Wu S, Zeng H, Sun F. Circulating tumor DNA as prognostic markers of relapsed breast cancer: a systematic review and meta-analysis. JOURNAL OF THE NATIONAL CANCER CENTER 2024; 4:63-73. [PMID: 39036387 PMCID: PMC11256521 DOI: 10.1016/j.jncc.2024.01.003] [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: 09/26/2023] [Revised: 01/02/2024] [Accepted: 01/16/2024] [Indexed: 07/23/2024] Open
Abstract
OBJECTIVE Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. METHODS PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. RESULTS A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50-0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04-0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73-12.17; relapse outcome: RR = 7.11, 95% CI: 3.05-16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12-3.70; post-operative: HR = 6.03, 95% CI: 1.31-27.78). CONCLUSIONS In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.
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Affiliation(s)
- Na'na Guo
- Hebei Province Centers for Disease Control and Prevention, Shijiazhuang, China
| | - Qingxin Zhou
- Tianjin Centers for Disease Control and Prevention, Tianjin, China
| | - Xiaowei Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Baoqi Zeng
- Department of Science and Education, Peking University Binhai Hospital, Tianjin, China
| | - Shanshan Wu
- Clinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hongmei Zeng
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Major Disease Epidemiology, Ministry of Education (Peking University), Beijing, China
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Wojakowska A, Marczak L, Zeman M, Chekan M, Zembala-Nożyńska E, Polanski K, Strugała A, Widlak P, Pietrowska M. Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy. Front Oncol 2024; 14:1323961. [PMID: 38410100 PMCID: PMC10896604 DOI: 10.3389/fonc.2024.1323961] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 01/16/2024] [Indexed: 02/28/2024] Open
Abstract
Background Neoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients' quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue. Methods Here, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT. Results The integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients. Conclusion We proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.
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Affiliation(s)
- Anna Wojakowska
- Laboratory of Mass Spectrometry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland
| | - Lukasz Marczak
- Laboratory of Mass Spectrometry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland
| | - Marcin Zeman
- The Oncologic and Reconstructive Surgery Clinic, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
| | - Mykola Chekan
- Department of Pathomorphology, University of Technology, Katowice, Poland
| | - Ewa Zembala-Nożyńska
- Tumor Pathology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
| | | | - Aleksander Strugała
- Laboratory of Mass Spectrometry, Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznan, Poland
| | - Piotr Widlak
- 2nd Department of Radiology, Medical University of Gdańsk, Gdańsk, Poland
| | - Monika Pietrowska
- Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice, Poland
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20
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Zeng Z, Ma D, Zhu P, Niu K, Fu S, Di X, Zhu J, Xie P. Prognostic value of the ratio of pretreatment carcinoembryonic antigen to tumor volume in rectal cancer. J Gastrointest Oncol 2023; 14:2395-2408. [PMID: 38196531 PMCID: PMC10772672 DOI: 10.21037/jgo-23-683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 11/10/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND As a commonly used biomarker in rectal cancer (RC), the prognostic value of carcinoembryonic antigen (CEA) remains underexplored. This study aims to evaluate the prognostic value of pretreatment CEA/tumor volume in RC. METHODS This retrospective study included patients who underwent pretreatment magnetic resonance imaging (MRI) with histologically confirmed primary rectal adenocarcinoma from November 2012 to April 2018. Patients were divided into high-risk and low-risk groups according to the median values of CEA/Diapath (CEA to pathological diameter), CEA/DiaMRI (CEA to MRI tumor diameter), and CEA/VolMRI (CEA to MRI tumor volume). Cox regression analysis was utilized to determine the prognostic value of CEA, CEA/Diapath, CEA/DiaMRI, and CEA/VolMRI. Stepwise regression was used to establish nomograms for predicting disease-free survival (DFS) and overall survival (OS). Predictive performance was estimated by using the concordance index (C-index) and area under curve receiver operating characteristic (AUC). RESULTS A total of 343 patients [median age 58.99 years, 206 (60.06%) males] were included. After adjusting for patient-related and tumor-related factors, CEA/VolMRI was superior to CEA, CEA/Diapath, and CEA/DiaMRI in distinguishing high-risk from low-risk patients in terms of DFS [hazard ratio (HR) =1.83; P=0.010] and OS (HR =1.67; P=0.048). Subanalysis revealed that CEA/VolMRI stratified high death risk in CEA-negative individuals (HR =2.50; P=0.038), and also stratified low recurrence risk in CEA-positive individuals (HR =2.06; P=0.024). In the subanalysis of stage II or III cases, the highest HRs and the smallest P values were observed in distinguishing high-risk from low-risk patients according to CEA/VolMRI in terms of DFS (HR =2.44; P=0.046 or HR =2.41; P=0.001) and OS (HR =1.96; P=0.130 or HR =2.22; P=0.008). The nomograms incorporating CEA/VolMRI showed good performance, with a C-index of 0.72 [95% confidence interval (CI): 0.68-0.79] for DFS and 0.73 (95% CI: 0.68-0.80) for OS. CONCLUSIONS Higher CEA/VolMRI was associated with worse DFS and OS. CEA/VolMRI was superior to CEA, CEA/Diapath, and CEA/DiaMRI in predicting DFS and OS. Pretreatment CEA/VolMRI may facilitate risk stratification and treatment decision-making.
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Affiliation(s)
- Zhiming Zeng
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Decai Ma
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pan Zhu
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Kexin Niu
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shuai Fu
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaohui Di
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junying Zhu
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Peiyi Xie
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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21
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Wang R, Wang Q, Li P. Significance of carcinoembryonic antigen detection in the early diagnosis of colorectal cancer: A systematic review and meta-analysis. World J Gastrointest Surg 2023; 15:2907-2918. [PMID: 38222002 PMCID: PMC10784816 DOI: 10.4240/wjgs.v15.i12.2907] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 09/30/2023] [Accepted: 11/14/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a prevalent malignant tumor involving adenomas that develop into malignant lesions. Carcinoembryonic antigen (CEA) is a non-specific serum biomarker upregulated in CRC. The concentration of CEA is modulated by tumor stage and grade, tumor site in the colon, ploidy status, and patient smoking status. This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults. AIM To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults. METHODS A systematic search was performed using four databases: MEDLINE, Cochrane Trials, EMBASE, and the Web of Science. The inclusion criteria were as follows: Adult patients aged ≥ 18 years who had completed CRC curative treatment and were followed up postoperatively; reporting the number of CRC recurrences as an outcome; and randomized, clinical, cohort, and case-control study designs. Studies that were not published in English and animal studies were excluded. The following data were extracted by three independent reviewers: Study design, index tests, follow-up, patient characteristics, and primary outcomes. All statistical analyses were performed using the RevMan 5.4.1. RESULTS A total of 3232 studies were identified, with 73 remaining following the elimination of duplicates. After screening on predetermined criteria, 12 studies were included in the final analysis. At a reference standard of 5 mg/L, CEA detected only approximately half of recurrent CRCs, with a pooled sensitivity of 59% (range, 33%-83%) and sensitivity of 89% (range, 58%-97%). CONCLUSION CEA is a significant marker for CRC diagnosis. However, it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence, with an essential proportion of false negatives.
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Affiliation(s)
- Rui Wang
- Department of Nuclear Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
| | - Qin Wang
- Delivery Room, Chengdu Women’s and Children’s Central Hospital, Chengdu 610000, Sichuan Province, China
| | - Pan Li
- Department of Nuclear Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
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22
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Bhagat A, Lyerly HK, Morse MA, Hartman ZC. CEA vaccines. Hum Vaccin Immunother 2023; 19:2291857. [PMID: 38087989 PMCID: PMC10732609 DOI: 10.1080/21645515.2023.2291857] [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: 09/13/2023] [Accepted: 12/02/2023] [Indexed: 12/18/2023] Open
Abstract
Carcinoembryonic antigen (CEA) is a glycosylated cell surface oncofetal protein involved in adhesion, proliferation, and migration that is highly upregulated in multiple carcinomas and has long been a promising target for cancer vaccination. This review summarizes the progress to date in the development of CEA vaccines, examining both pre-clinical and clinical studies across a variety of vaccine platforms that in aggregate, begin to reveal some critical insights. These studies demonstrate the ability of CEA vaccines to break immunologic tolerance and elicit CEA-specific immunity, which associates with improved clinical outcomes in select individuals. Approaches that have combined replicating viral vectors, with heterologous boosting and different adjuvant strategies have been particularly promising but, these early clinical trial results will require confirmatory studies. Collectively, these studies suggest that clinical efficacy likely depends upon harnessing a potent vaccine combination in an appropriate clinical setting to fully realize the potential of CEA vaccination.
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Affiliation(s)
- Anchit Bhagat
- Department of Surgery, Division of Surgical Sciences, Duke University, Durham, NC, USA
| | - Herbert K. Lyerly
- Department of Surgery, Division of Surgical Sciences, Duke University, Durham, NC, USA
- Department of Pathology, Duke University, Durham, NC, USA
- Department of Integrative Immunobiology, Duke University, Durham, NC, USA
| | - Michael A. Morse
- Department of Surgery, Division of Surgical Sciences, Duke University, Durham, NC, USA
- Department of Medicine, Duke University, Durham, NC, USA
| | - Zachary C. Hartman
- Department of Surgery, Division of Surgical Sciences, Duke University, Durham, NC, USA
- Department of Pathology, Duke University, Durham, NC, USA
- Department of Integrative Immunobiology, Duke University, Durham, NC, USA
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23
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Fox J, Batchelor DVB, Roberts H, Moorcroft SC, Valleley EM, Coletta PL, Evans SD. Gold Nanotapes and Nanopinecones in a Quantitative Lateral Flow Assay for the Cancer Biomarker Carcinoembryonic Antigen. ACS APPLIED NANO MATERIALS 2023; 6:17769-17777. [PMID: 37854850 PMCID: PMC10580237 DOI: 10.1021/acsanm.3c03053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/04/2023] [Indexed: 10/20/2023]
Abstract
Colorectal cancer is the third most common malignancy and the second leading cause of cancer death globally. Multiple studies have linked levels of carcinoembryonic antigen in patient serum to poor disease prognosis. Hence, the ability to detect low levels of carcinoembryonic antigen has applications in earlier disease diagnosis, assessment, and recurrence monitoring. Existing carcinoembryonic antigen detection methods often require multiple reagents, trained operators, or complex procedures. A method alleviating these issues is the lateral flow assay, a paper-based platform that allows the detection and quantification of target analytes in complex mixtures. The tests are rapid, are point-of-care, possess a long shelf life, and can be stored at ambient conditions, making them ideal for use in a range of settings. Although lateral flow assays typically use spherical gold nanoparticles to generate the classic red signal, recent literature has shown that alternate morphologies to spheres can improve the limit of detection. In this work, we report the application of alternative gold nanoparticle morphologies, gold nanotapes (∼35 nm in length) and gold nanopinecones (∼90 nm in diameter), in a lateral flow assay for carcinoembryonic antigen. In a comparative assay, gold nanopinecones exhibited a ∼2× improvement in the limit of detection compared to commercially available spherical gold nanoparticles for the same antibody loading and total gold content, whereas the number of gold nanopinecones in each test was ∼3.2× less. In the fully optimized test, a limit of detection of 14.4 pg/mL was obtained using the gold nanopinecones, representing a 24-fold improvement over the previously reported gold-nanoparticle-based carcinoembryonic antigen lateral flow assay.
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Affiliation(s)
- Joseph Fox
- Molecular
and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, United Kingdom
| | - Damien V. B. Batchelor
- Molecular
and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, United Kingdom
| | - Holly Roberts
- Molecular
and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, United Kingdom
| | - Samuel C.T. Moorcroft
- Molecular
and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, United Kingdom
| | - Elizabeth M.A. Valleley
- Leeds
Institute of Medical Research, Wellcome Trust Brenner Building, St James’s University Hospital, Leeds LS9 7TF, United Kingdom
| | - Patricia Louise Coletta
- Leeds
Institute of Medical Research, Wellcome Trust Brenner Building, St James’s University Hospital, Leeds LS9 7TF, United Kingdom
| | - Stephen D. Evans
- Molecular
and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, United Kingdom
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Hu R, Li X, Zhou X, Ding S. Development and validation of a competitive risk model in patients with rectal cancer: based on SEER database. Eur J Med Res 2023; 28:362. [PMID: 37735712 PMCID: PMC10515244 DOI: 10.1186/s40001-023-01357-3] [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: 08/17/2023] [Accepted: 09/10/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Rectal cancer is one of the most common malignancies. To predict the specific mortality risk of rectal cancer patients, we constructed a predictive nomogram based on a competing risk model. METHODS The information on rectal cancer patients was extracted from the SEER database. Traditional survival analysis and specific death analysis were performed separately on the data. RESULTS The present study included 23,680 patients, with 16,580 in the training set and 7100 in the validation set. The specific mortality rate calculated by the competing risk model was lower than that of the traditional survival analysis. Age, Marriage, Race, Sex, ICD-O-3Hist/Behav, Grade, AJCC stage, T stage, N stage, Surgery, Examined LN, RX SUMM-SURG OTH, Chemotherapy, CEA, Deposits, Regional nodes positive, Brain, Bone, Liver, Lung, Tumor size, and Malignant were independent influencing factors of specific death. The overall C statistic of the model in the training set was 0.821 (Se = 0.001), and the areas under the ROC curve for cancer-specific survival (CSS) at 1, 3, and 5 years were 0.842, 0.830, and 0.812, respectively. The overall C statistic of the model in the validation set was 0.829 (Se = 0.002), and the areas under the ROC curve for CSS at 1, 3, and 5 years were 0.851, 0.836, and 0.813, respectively. CONCLUSIONS The predictive nomogram based on a competing risk model for time-specific mortality in patients with rectal cancer has very desirable accuracy. Thus, the application of the predictive nomogram in clinical practice can help physicians make clinical decisions and follow-up strategies.
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Affiliation(s)
- Ruobing Hu
- Department of Gastroenterology and Hepatology, People's Hospital of Zhengzhou University, No.7 Weiwu Road, Zhengzhou, 450003, Henan, China
| | - Xiuling Li
- Department of Gastroenterology and Hepatology, People's Hospital of Zhengzhou University, No.7 Weiwu Road, Zhengzhou, 450003, Henan, China
| | - Xiaomin Zhou
- Department of Infection Disease, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, China
| | - Songze Ding
- Department of Gastroenterology and Hepatology, People's Hospital of Zhengzhou University, No.7 Weiwu Road, Zhengzhou, 450003, Henan, China.
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Mikuni Y, Tani M, Ichikawa N, Matsui H, Emoto S, Yoshida T, Otsuka T, Homma S, Norihiko T, Taketomi A. Early-stage sigmoid colon cancer resection followed by liver metastasis recurrence 1 year later and mesenteric recurrence more than 5 years later: a case report. Surg Case Rep 2023; 9:151. [PMID: 37650976 PMCID: PMC10471527 DOI: 10.1186/s40792-023-01731-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 08/10/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND Early-stage colorectal cancer (CRC) is often treated endoscopically, but additional surgical resection may be considered depending on pathological findings. CASE PRESENTATION A 73-year-old man was found to have early-stage sigmoid colon cancer by colonoscopy during a medical examination, and endoscopic mucosal resection (EMR) was performed. The lesion was a 7-mm-sized sessile polyp, and the pathological diagnosis was well-differentiated tubular adenocarcinoma, pT1 (submucosal invasion of 400 μm), with no lymphovascular invasion, low budding grade, and negative horizontal and vertical margins. Therefore, the patient was observed without postoperative treatment. One year later, a computed tomography (CT) scan showed multiple liver metastases. After five courses of preoperative chemotherapy with folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and panitumumab, liver metastases were reduced. The patient underwent extended right hepatic lobectomy. The pathological finding was well-to-moderately differentiated tubular adenocarcinoma, and immunohistochemistry findings were consistent with liver metastases from sigmoid colon cancer. Postoperatively, the patient received five courses adjuvant chemotherapy with FOLFOX. Although the patient had been recurrence-free for 5 years after liver resection, a CT scan revealed a nodular lesion in the sigmoid mesentery. Positron emission tomography (PET) showed abnormal accumulation in the same lesion. Therefore, the mesenteric nodules diagnosed as lymph metastasis and recurrence of sigmoid colon cancer and performed laparoscopic sigmoid colon resection with lymph node dissection. The pathological findings showed that the recurrent lesion in the mesentery formed a nodular infiltrate with venous, lymphatic, and neural invasion, but lymph node structures were not found, and it was assumed to be metastasis or recurrence due to lymphovascular invasion. The pathologic specimen of the sigmoid colon had no neoplastic lesions, which are considered to be a local recurrence on the mucosal surface. After sigmoid colectomy, adjuvant chemotherapy with CapeOX was conducted, and the patient has been recurrence-free for 13 months at present. CONCLUSION Even early-stage CRCs that have no pathological indications for additional resection have risks of metastases and recurrences, and we may need to consider that the criteria for additional resection should not be limited to pathological findings alone.
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Affiliation(s)
- Yumeto Mikuni
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Michio Tani
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Nobuki Ichikawa
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Hiroki Matsui
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Shin Emoto
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Tadashi Yoshida
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Takuya Otsuka
- Department of Surgical Pathology, Hokkaido University Hospital, North 14 West 5, Kita-ku, Sapporo, Hokkaido 060-8648 Japan
| | - Shigenori Homma
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Takahashi Norihiko
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
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Zhang E, Ding C, Li S, Aikemu B, Zhou X, Fan X, Sun J, Yang X, Zheng M. Polyamine metabolism patterns characterized tumor microenvironment, prognosis, and response to immunotherapy in colorectal cancer. Cancer Cell Int 2023; 23:96. [PMID: 37202800 DOI: 10.1186/s12935-023-02892-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 03/06/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND Changes in Polyamine metabolism (PAM) have been shown to establish a suppressive tumor microenvironment (TME) and substantially influence the progression of cancer in the recent studies. However, newly emerging data have still been unable to fully illuminate the specific effects of PAM in human cancers. Here, we analyzed the expression profiles and clinical relevance of PAM genes in colorectal cancer (CRC). METHODS Based on unsupervised consensus clustering and principal component analysis (PCA) algorithm, we designed a scoring model to evaluate the prognosis of CRC patients and characterize the TME immune profiles, with related independent immunohistochemical validation cohort. Through comparative profiling of cell communities defined by single cell sequencing data, we identified the distinct characteristics of polyamine metabolism in the TME of CRC. RESULTS Three PAM patterns with distinct prognosis and TME features were recognized from 1224 CRC samples. Moreover, CRC patients could be divided into high- and low-PAMscore subgroups by PCA-based scoring system. High PAMscore subgroup were associated to more advanced stage, higher infiltration level of immunosuppressive cells, and unfavorable prognosis. These results were also validated in CRC samples from other public CRC datasets and our own cohort, which suggested PAM genes were ideal biomarkers for predicting CRC prognosis. Notably, PAMscore also corelated with microsatellite instability-high (MSI-H) status, higher tumor mutational burden (TMB), and increased immune checkpoint gene expression, implying a potential role of PAM genes in regulating response to immunotherapy. To further confirm above results, we demonstrated a high-resolution landscape of TME and cell-cell communication network in different PAM patterns using single cell sequencing data and found that polyamine metabolism affected the communication between cancer cells and several immune cells such as T cells, B cells and myeloid cells. CONCLUSION In total, our findings highlighted the significance of polyamine metabolism in shaping the TME and predicting the prognosis of CRC patients, providing novel strategies for immunotherapy and the targeting polyamine metabolites.
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Affiliation(s)
- Enkui Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Chengsheng Ding
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Shuchun Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Batuer Aikemu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Xueliang Zhou
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Xiaodong Fan
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Jing Sun
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
| | - Xiao Yang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
- Department of General Surgery & Carson International Cancer Research Center, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy, Shenzhen, 518055, China.
| | - Minhua Zheng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
- Department of General Surgery & Carson International Cancer Research Center, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy, Shenzhen, 518055, China.
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Mobach L, Rapee RM, Klein AM. The Role of Distorted Cognitions in Mediating Treatment Outcome in Children with Social Anxiety Disorder: A Preliminary Study. Child Psychiatry Hum Dev 2023; 54:558-569. [PMID: 34674074 PMCID: PMC9977708 DOI: 10.1007/s10578-021-01268-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2021] [Indexed: 11/30/2022]
Abstract
This study examined whether distorted cognition changes during cognitive behavioural therapy (CBT) in children (N = 61; aged 7-12) with social anxiety disorder (SAD) and whether changes in distorted cognition from pre- to post-treatment predict SAD at 6-month follow-up. Baseline distorted cognition was also examined as a predictor of post-treatment outcome. Multiple informant SAD-measures were obtained pre-treatment, post-treatment and at 6-month follow-up. Children reported on interpretation bias and dysfunctional beliefs. A decrease in interpretation bias and dysfunctional beliefs was prospectively related to greater SAD change between post-treatment and 6-month follow-up. Child-reported SAD-change at post-treatment predicted greater change in dysfunctional beliefs at 6-month follow-up. Higher baseline interpretation bias predicted greater change in SAD-severity at post-treatment. Children with greater distorted cognition reductions during treatment, showed greater treatment gains at 6-month follow-up. Children who do not show this reduction may require additional efforts focused on distorted cognition to maximally benefit from treatment.
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Affiliation(s)
- Lynn Mobach
- Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, NSW, 2109, Australia.
- Department of Clinical Psychology, Behavioural Science Institute, Radboud University, Montessorilaan 3, 6525 HR, Nijmegen, the Netherlands.
| | - Ronald M Rapee
- Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, NSW, 2109, Australia
| | - Anke M Klein
- Department of Clinical Psychology, Behavioural Science Institute, Radboud University, Montessorilaan 3, 6525 HR, Nijmegen, the Netherlands
- Unit Developmental and Educational Psychology, Institute of Psychology, Leiden University, Leiden, the Netherlands
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28
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Li Y, Hu S, Chen C, Alifu N, Zhang X, Du J, Li C, Xu L, Wang L, Dong B. Opal photonic crystal-enhanced upconversion turn-off fluorescent immunoassay for salivary CEA with oral cancer. Talanta 2023; 258:124435. [PMID: 36940576 DOI: 10.1016/j.talanta.2023.124435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/26/2023] [Accepted: 03/07/2023] [Indexed: 03/16/2023]
Abstract
The point-of-care test of tumor markers in saliva with high specificity and sensitivity for early diagnosis of oral cancer is of great interest and significance, but remaining a daunting challenge due to the low concentration of such biomarkers in oral fluid. Herein, a turn-off biosensor based on opal photonic crystal (OPC) enhanced upconversion fluorescence is proposed to detect the carcinoembryonic antigen (CEA) in saliva by applying fluorescence resonance energy transfer sensing strategy. Hydrophilic PEI ligands are modified on upconversion nanoparticles to enhance the sensitivity of biosensor by promoting sufficient contact between saliva and detection region. As a substrate for the biosensor, OPC can also provide a local-field effect for greatly enhanced upconversion fluorescence by coupling the stop band and excitation light, and a 66-fold amplification of the upconversion fluorescence signal was obtained. For the CEA detection in spiked saliva, such sensors showed a favorable linear relationship at 0.1-2.5 ng mL-1 and more than 2.5 ng mL-1, respectively. The limit of detection was down to 0.1 ng mL-1. Moreover, by monitoring real saliva, the effective discrepancy between patients and healthy people was confirmed, indicating remarkable practical application value in clinical early diagnosis and home-based self-monitoring of tumors.
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Affiliation(s)
- Yige Li
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China
| | - Songtao Hu
- State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130021, China
| | - Cong Chen
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China
| | - Nuernisha Alifu
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, 830011, China
| | - Xueliang Zhang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, 830011, China
| | - Juanrui Du
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China
| | - Chunyan Li
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China
| | - Lin Xu
- State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130021, China
| | - Lin Wang
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China.
| | - Biao Dong
- State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130021, China.
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Desai S, Guddati AK. Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Cancer Antigen 125, Prostate-Specific Antigen and Other Cancer Markers: A Primer on Commonly Used Cancer Markers. World J Oncol 2023; 14:4-14. [PMID: 36895994 PMCID: PMC9990734 DOI: 10.14740/wjon1425] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 11/28/2022] [Indexed: 03/01/2023] Open
Abstract
Cancer markers are molecules produced by cancer cells which may serve to identify the presence of cancer. Cancer markers can be differentiated as serum-based, radiology-based and tissue-based, and are one of the most important tools in diagnosing, staging and monitoring of treatment of many cancers. The most used cancer markers are serum cancer markers due to its relative ease and lower cost of testing. However, serum cancer markers have poor mass screening utilization due to poor positive predictive value. Several markers such as prostate-specific antigen (PSA), beta-human chorionic gonadotropin (B-hCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are used to aid in diagnosis of cancer in cases of high suspicion. Serum markers such as carcinoembryonic antigen (CEA), AFP, carbohydrate antigen 19-9 (CA 19-9), and 5-hydroxyindoleacetic acid (5-HIAA) play a significant role in assessing disease prognosis as well as response to treatment. This work reviews the role of some of the biomarkers in the diagnosis and treatment of cancer.
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Affiliation(s)
- Shreya Desai
- Division of Hematology/Oncology, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA
| | - Achuta K Guddati
- Division of Hematology/Oncology, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA
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30
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Lee JO, Kim M, Lee JH, Kim Y, Lim HK, Kwon YH, Shin R, Park JW, Ryoo SB, Park KJ, Jeong SY. Carbohydrate antigen 19-9 plus carcinoembryonic antigen for prognosis in colorectal cancer: An observational study. Colorectal Dis 2023; 25:272-281. [PMID: 36226485 DOI: 10.1111/codi.16372] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/24/2022] [Accepted: 09/29/2022] [Indexed: 02/08/2023]
Abstract
AIM Carcinoembryonic antigen (CEA) is a primary prognostic marker and can detect colorectal cancer (CRC) recurrence; however, it has low sensitivity. Carbohydrate antigen 19-9 (CA 19-9) can be used as a supplemental tumour marker along with CEA. The purpose of this study was to determine whether preoperative CA 19-9 added to CEA helped predict long-term prognosis and whether follow-up CA 19-9 added to CEA had additional benefits in diagnosing the recurrence of CRC. METHOD We retrospectively assessed patients who underwent surgery for primary CRC between January 2004 and December 2015 at Seoul National University Hospital. Data on demographics, preoperative and follow-up CEA and CA 19-9 levels, recurrence and survival were obtained and analysed with respect to tumour marker levels to ascertain their prognostic and diagnostic values. RESULTS A total of 4972 and 1530 patients were included to analyse preoperative and follow-up tumour marker levels, respectively. The 5-year relapse-free survival rates were 72.2% ± 0.8%, 52.5% ± 2.2%, 55.5% ± 3.2% and 32.1% ± 2.3% in the normal CEA and CA 19-9, high CEA, high CA 19-9, and high CEA and high CA 19-9 groups, respectively (all P < 0.001). Patients whose elevated CEA or CA 19-9 levels reduced to normal levels had better survival outcomes than those with postoperatively elevated levels. Elevated follow-up CA 19-9 and CEA levels were related to higher incidences of distant metastasis (CA 19-9, 14.0% vs. 23.1%, P = 0.004; CEA, 12.6% vs. 30.1%, P < 0.001) but not to local recurrence. Combined follow-up CEA and CA 19-9 increased the sensitivity for recurrence to 31.4%, with a 5% difference from the sensitivity of CEA alone. In the subgroup with high preoperative CA 19-9 levels, sensitivity increased by 18.2% overall. CONCLUSION CA 19-9 is a valuable prognostic and diagnostic marker for CRC when used adjunctively with CEA and can be a supplementary marker with CEA to improve sensitivity, especially with elevated preoperative CA 19-9.
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Affiliation(s)
- Jong O Lee
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea
| | - Minjung Kim
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Jeong-Hwan Lee
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea
| | - Youngmin Kim
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea
| | - Han-Ki Lim
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea
| | - Yoon-Hye Kwon
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea
| | - Rumi Shin
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea.,Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Ji W Park
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea
| | - Kyu J Park
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea
| | - Seung-Yong Jeong
- Department of Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.,Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea
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31
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Zhan Y, Wang S, Yuan Z, Zhao X, Ni K, Xin R, Zhou X, Liu Z, Yin X, Ping H, Liu Y, Wang W, Yan S, Han Q, Zhang X, Zhang Q, Liu Y, Zhang C. The stool syndecan2 methylation test is more robust than blood tests for methylated septin9, CEA, CA19-9 and CA724: a diagnostic test for the early detection of colorectal neoplasms. Transl Cancer Res 2023; 12:65-77. [PMID: 36760372 PMCID: PMC9906059 DOI: 10.21037/tcr-22-1710] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 11/17/2022] [Indexed: 01/11/2023]
Abstract
Background Methylated syndecan2 (mSDC2) in stool samples has been found to be associated with colorectal cancer (CRC) and precancerous lesions. However, the available data are limited, and no previous studies have compared the analysis of mSDC2 with other diagnostic tests. Thus, we aimed to evaluate the clinical performance of a stool mSDC2 test and compare its performance with that of blood-based tests for methylated septin9 (mSEPT9), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 724 (CA724) in detecting colorectal neoplasms. Methods The gold standard diagnostic technique that was used was colonoscopy combined with a pathological analysis of biopsied tissue. Stool DNA was extracted from 1,002 stool samples (445 from CRCs, 115 from adenomas, and 442 from controls) and then bisulfite-converted, followed by real-time quantitative methylation-specific polymerase chain reaction. Blood mSEPT9 levels were quantified by the Epi proColon 2.0 assay, and serum CEA, CA19-9 and CA724 levels were measured by electrochemiluminescence. The main indexes used during the evaluation were sensitivity, specificity and the area under the receiver operating characteristic curve (AUC). Results Stool mSDC2 detected 69.7% of CRCs, which was significantly higher than 53.8% by plasma mSEPT9, 37.2% by CEA, 13.1% by CA19-9 and 17.5% by CA724; for adenoma, the detection rates were 31.3%, 11.1%, 2.3% and 11.9%, respectively. The AUC of mSDC2 in detecting CRC was 0.83, compared to 0.72, 0.75, 0.63 and 0.54 for mSEPT9, CEA, CA19-9 and CA724, respectively. mSDC2 identified patients with stage I-III CRC with a sensitivity of 71.6%, which was significantly higher than that of mSEPT9, CEA, CA19-9 and CA724 (54.2%, 35.5%, 11.9%, and 15.0%, respectively); for stage IV CRC, the sensitivities of mSDC2, mSEPT9, CEA, CA19-9 and CA724 were 75.9%, 82.6%, 79.3%, 36.0% and 56.5%, respectively. SDC2 and CEA had a significantly higher sensitivity for distal CRC than for proximal CRC. Conclusions The stool SDC2 methylation test had a better performance in detecting nonmetastatic CRC and adenoma than evaluations of mSEPT9, CEA, CA19-9 and CA724 in blood. Our findings could be used to modify approaches for CRC prevention and early detection.
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Affiliation(s)
- Yixiang Zhan
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;,School of Medicine, Nankai University, Tianjin, China
| | - Shuyuan Wang
- School of Medicine, Nankai University, Tianjin, China
| | - Zhen Yuan
- School of Medicine, Nankai University, Tianjin, China
| | - Xuanzhu Zhao
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;,School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Kemin Ni
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;,School of Medicine, Nankai University, Tianjin, China
| | - Ran Xin
- School of Medicine, Nankai University, Tianjin, China
| | - Xingyu Zhou
- School of Medicine, Nankai University, Tianjin, China
| | - Zhaoce Liu
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;,School of Medicine, Nankai University, Tianjin, China
| | - Xin Yin
- School of Medicine, Nankai University, Tianjin, China
| | - Hangyu Ping
- School of Medicine, Nankai University, Tianjin, China
| | - Yaohong Liu
- School of Medicine, Nankai University, Tianjin, China
| | - Wanting Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Suying Yan
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qiurong Han
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xipeng Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;,The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China;,Tianjin Institute of Coloproctology, Tianjin, China
| | - Qinghuai Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;,The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China;,Tianjin Institute of Coloproctology, Tianjin, China
| | - Yandi Liu
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin, China
| | - Chunze Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;,The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China;,Tianjin Institute of Coloproctology, Tianjin, China
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Wang K, Ma L, Chen L, Jiang Y, Liu N, Cai J, Zhang Y. The clinical value of a nomogram constructed from CEA, CA199, PT, FIB, tumor differentiation and TNM stage in colorectal cancer. Cancer Biomark 2023; 38:537-549. [PMID: 37980649 DOI: 10.3233/cbm-230116] [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] [Indexed: 11/21/2023]
Abstract
BACKGROUND The accurate Tumor-Node-Metastasis (TNM) staging of colorectal cancer (CRC) is of great guiding significance for the judgment of tumor progression and prognosis, and the formulation of treatment strategies. OBJECTIVE The aim of this study was to construct a recurrence risk scoring (RRS) system and prognostic prediction model to improve the accuracy of staging, prognosis prediction, and clinical decision making in resectable CRC. METHODS CRC patients who underwent radical resection were retrospectively enrolled into study. Multivariable Cox regression model was applied to screen for independent prognostic factors. The RRS system is composed of independent prognostic factors which was awarded 1point each. A prognostic model composed of RRS and TNM staging system (RRS-TNM model) was applied to predict postoperative recurrence. RESULTS TNM stage, tumor differentiation, preoperative elevated Carcinoembryonic Antigen, Carbohydrate Antigen 199, Prothrombin Time and Fibrinogen were the independent prognostic biomarkers. 173 of 540 patients had recurrence. The 5-year cumulative recurrence rate (5-y CRR) and disease-free survival (DFS) of postoperative p-TNM stage I, II, and III were 12.7% and 104.8 months, 26.5% and 89.3 months, and 55.5% and 57.3 months, respectively. The 5-y CRR and DFS of preoperative Low-risk (RRS 0-1score), Middle-risk (RRS 2-3scores), and High-risk (RRS 4-5scores) groups were 13.9% and 101.1 months, 40.9% and 75.5 months, and 70.2% and 41.1 months. The AUC (area under ROC curve) of RRS system was not inferior to that of TNM staging system (0.713 vs. 0.666; P= 0.093). The AUC (0.770) and C-index value (0.721) of RRS-TNM model were significantly better than both RRS and TNM staging system (P< 0.001). CONCLUSIONS The RRS system accurately identifies CRC patients with high-risk recurrence preoperatively. Constructing a nomogram using the RRS system and TNM staging significantly improves the accuracy of staging and prognosis prediction, which is of great clinical significance for individualized clinical treatment and follow-up of CRC.
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Affiliation(s)
- Kang Wang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Lulu Ma
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Liying Chen
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Yatong Jiang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Ningquan Liu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Jianchun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Yiyao Zhang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
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Wei Z, Luciano K, Xia X. Catalytic Gold-Iridium Nanoparticles as Labels for Sensitive Colorimetric Lateral Flow Assay. ACS NANO 2022; 16:21609-21617. [PMID: 36448915 DOI: 10.1021/acsnano.2c10574] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
The colorimetric lateral flow assay (CLFA, also known as test strip) is a widely used point-of-care diagnostic technology. It has been a challenge to significantly improve the detection sensitivity of CLFA without involving additional equipment and/or compromising its simplicity. In this work, we break through the detection limit barrier of CLFA by developing a type of catalytic nanoparticles (NPs) used as labels. Specifically, the NPs were engineered by coating conventional gold NPs (AuNPs) with iridium (Ir) to form an Au-Ir core-shell structure. Such Au-Ir NPs possess ultrahigh peroxidase-like catalytic activities. A single Au-Ir NP can generate up to 107 colored molecules per second by catalyzing peroxidase substrates. The strong color signal from the catalysis ensures a high sensitivity of associated CLFA. The Au-Ir NP-based CLFA was successfully applied to the detection of two different cancer biomarkers that achieved limits of detection at the low picogram per milliliter level, hundreds of times lower than those of conventional AuNP-based CLFA.
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Affiliation(s)
- Zhiyuan Wei
- Department of Chemistry, University of Central Florida, Orlando, Florida 32816, United States
| | - Keven Luciano
- Department of Chemistry, University of Central Florida, Orlando, Florida 32816, United States
| | - Xiaohu Xia
- Department of Chemistry, University of Central Florida, Orlando, Florida 32816, United States
- NanoScience Technology Center, University of Central Florida, Orlando, Florida 32816, United States
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Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters. Cancers (Basel) 2022; 14:cancers14246238. [PMID: 36551723 PMCID: PMC9777013 DOI: 10.3390/cancers14246238] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 12/06/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
Complete pathological response (pCR) is achieved in 10−20% of rectal cancers when treated with short-course radiotherapy (scRT) or long-course chemoradiotherapy (CRT) and in 28% with total neoadjuvant therapy (scRT/CRT + CTX). pCR is associated with better outcomes and a “watch-and-wait” strategy (W&W). The aim of this study was to identify baseline clinical or imaging factors predicting pCR. All patients with preoperative treatment and delays to surgery in Uppsala-Dalarna (n = 359) and Stockholm (n = 635) were included. Comparison of pCR versus non-pCR was performed with binary logistic regression models. Receiver operating characteristics (ROC) models for predicting pCR were built using factors with p < 0.10 in multivariate analyses. A pCR was achieved in 12% of the 994 patients (scRT 8% [33/435], CRT 13% [48/358], scRT/CRT + CTX 21% [43/201]). In univariate and multivariate analyses, choice of CRT (OR 2.62; 95%CI 1.34−5.14, scRT reference) or scRT/CRT + CTX (4.70; 2.23−9.93), cT1−2 (3.37; 1.30−8.78; cT4 reference), tumour length ≤ 3.5 cm (2.27; 1.24−4.18), and CEA ≤ 5 µg/L (1.73; 1.04−2.90) demonstrated significant associations with achievement of pCR. Age < 70 years, time from radiotherapy to surgery > 11 weeks, leucocytes ≤ 109/L, and thrombocytes ≤ 4009/L were significant only in univariate analyses. The associations were not fundamentally different between treatments. A model including T-stage, tumour length, CEA, and leucocytes (with scores of 0, 0.5, or 1 for each factor, maximum 4 points) showed an area under the curve (AUC) of 0.66 (95%CI 0.60−0.71) for all patients, and 0.65−0.73 for the three treatments separately. The choice of neoadjuvant treatment in combination with low CEA, short tumour length, low cT-stage, and normal leucocytes provide support in predicting pCR and, thus, could offer guidance for selecting patients for organ preservation.
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Wolf RT, Jeppesen P, Pedersen MMA, Puggaard LB, Thastum M, Bilenberg N, Thomsen PH, Silverman WK, Plessen KJ, Neumer SP, Correll CU, Pagsberg AK, Gyrd-Hansen D. Cost-effectiveness of a transdiagnostic psychotherapy program for youth with common mental health problems. BMC Health Serv Res 2022; 22:819. [PMID: 35739556 PMCID: PMC9229821 DOI: 10.1186/s12913-022-08187-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 06/08/2022] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVES Our objective was to evaluate the cost-effectiveness of the transdiagnostic psychotherapy program Mind My Mind (MMM) for youth with common mental health problems using a cost-utility analysis (CUA) framework and data from a randomized controlled trial. Furthermore, we analyzed the impact of the choice of informant for both quality-of-life reporting and preference weights on the Incremental Cost-Effectiveness Ratio (ICER). METHODS A total of 396 school-aged (6-16 years) youth took part in the 6-month trial carried out in Denmark. CUAs were carried out for the trial period and four one-year extrapolation scenarios. Costs were based on a combination of budget and self-reported costs. Youths and parents were asked to report on the youth's quality-of-life three times during the trial using the Child Health Utility 9D (CHU9D). Parental-reported CHU9D was used in the base case together with preference weights of a youth population. Analyses using self-reported CHU9D and preference weights of an adult population were also carried out. RESULTS The analysis of the trial period resulted in an ICER of €170,465. The analyses of the one-year scenarios resulted in ICERs between €23,653 and €50,480. The ICER increased by 24% and 71% compared to the base case when using self-reported CHU9D and adult preference weights, respectively. CONCLUSION The MMM intervention has the potential to be cost-effective, but the ICER is dependent on the duration of the treatment effects. Results varied significantly with the choice of informant and the choice of preference weights indicating that both factors should be considered when assessing CUA involving youth.
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Affiliation(s)
- Rasmus Trap Wolf
- Child and Adolescent Mental Health Center, Mental Health Services - Capital Region of Denmark, Copenhagen, Denmark.
- Danish Centre for Health Economics, Department of Public Health, University of Southern Denmark, Odense, Denmark.
| | - Pia Jeppesen
- Child and Adolescent Mental Health Center, Mental Health Services - Capital Region of Denmark, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Child and Adolescent Psychiatry, Copenhagen University Hospital - Psychiatry Region Zealand, Smedegade 16, 4000, Roskilde, Denmark
| | - Mette Maria Agner Pedersen
- Child and Adolescent Mental Health Center, Mental Health Services - Capital Region of Denmark, Copenhagen, Denmark
| | - Louise Berg Puggaard
- Child and Adolescent Mental Health Center, Mental Health Services - Capital Region of Denmark, Copenhagen, Denmark
| | - Mikael Thastum
- Centre for the Psychological Treatment of Children and Adolescents, Department of Psychology and Behavioural Sciences, Aarhus BSS, Aarhus University, Aarhus, Denmark
| | - Niels Bilenberg
- Department for Child and Adolescent Psychiatry, Mental Health Services in the Region of Southern Denmark, Odense, Denmark
- Institute of Clinical Medicine, University of Southern Denmark, Odense, Denmark
| | - Per Hove Thomsen
- Research Center at the Department for Child- and Adolescent Psychiatry, Aarhus University Hospital, Skejby, Denmark
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Wendy K Silverman
- Anxiety and Mood Disorders Program, Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA
| | - Kerstin Jessica Plessen
- Child and Adolescent Mental Health Center, Mental Health Services - Capital Region of Denmark, Copenhagen, Denmark
- Division of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - Simon-Peter Neumer
- Centre for Child and Adolescent Mental Health, Oslo, Norway
- The Arctic University of Norway, Centre for Child and Youth Mental Health and Child Welfare, North Norway (RKBU North), Tromsø, Norway
| | - Christoph U Correll
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY, USA
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
| | - Anne Katrine Pagsberg
- Child and Adolescent Mental Health Center, Mental Health Services - Capital Region of Denmark, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Dorte Gyrd-Hansen
- Danish Centre for Health Economics, Department of Public Health, University of Southern Denmark, Odense, Denmark
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Combined Efficacy of CXCL5, STC2, and CHI3L1 in the Diagnosis of Colorectal Cancer. JOURNAL OF ONCOLOGY 2022; 2022:7271514. [PMID: 35646113 PMCID: PMC9142324 DOI: 10.1155/2022/7271514] [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: 03/30/2022] [Accepted: 04/25/2022] [Indexed: 12/23/2022]
Abstract
Objective To improve the diagnostic capacity of serum biomarkers for colorectal cancer (CRC), we introduced three novel indicators, namely, the C-X-C motif chemokine ligand 5 (CXCL5), stanniocalcin 2 (STC2), and chitinase 3 like 1 (CHI3L1) and assessed their performances in the detection of CRC. Methods A total of 887 serum samples (153 health, 342 polyps, and 392 CRCs) were collected. Concentrations of CXCL5, STC2, and CHI3L1 were measured by the ELISA. CEA and CA199 were determined by electrochemiluminescence. Binary logistic regression was used to build the combination model. ROC analysis was used to evaluate the performance of biomarkers alone or in combination. Results Model_2 that based on CXCL5, STC2, and CHI3L1 was the best approach in discriminating CRC from non-CRC controls (AUC, 0.943 (0.922–0.960); sensitivity, 0.848; specificity, 0.917; and accuracy, 0.887 in the training cohort and 0.959 (95% CI 0.927–0.980), 0.878, 0.917, and 0.900 in the testing cohort, respectively). In the detection of early CRC, Model_2 revealed AUC, sensitivity, specificity, and accuracy of 0.925 (0.897–0.947), 0.793, 0.917, and 0.886 in the training cohort and those of 0.926 (0.979–0.959), 0.786, 0.931, and 0.898 in the testing cohort. Furthermore, Model_2 exhibited an excellent diagnostic performance in CEA-negative cases (0.938 (0.913–0.957), 0.826, 0.917, and 0.888 in the training cohort and 0.961 (0.925–0.983), 0.887, 0.931, and 0.918 in the testing cohort). As used alone, STC2 achieved the capacities that is second only to that of Model_2 (0.866 (0.837–0.892), 0.859, 0.842, and 0.853 in the training cohort and 0.887 (0.842–0.923), 0.922, 0.799, and 0.853 in the testing cohort). STC2 alone also yielded acceptable results for early CRC detection (0.815 (0.776–0.849), 0.767, 0.849, and 0.829 in the training cohort and 0.870 (0.812–0.914), 0.952, 0.799, and 0.833 in the testing cohort). Moreover, STC2 maintained diagnostic accuracy for CRC patients with negative CEA (0.874 (0.842–0.901), 0.862, 0.849, and 0.853 in the training cohort and 0.898 (0.848–0.936), 0.930, 0.801, and 0.842 in the testing cohort). In comparison, the performances of the CEA and CA199 based Model_1 were far from satisfactory, especially in early cases (0.767 (0.726–0.805), 0.491, 0.863, and 0.771 in the training cohort and 0.817 (0.754–0.870), 0.476, 0.889, and 0.796 in the testing cohort). Conclusions STC2 was a promising serum biomarker for CRC diagnosis either used alone or in combination with CXCL5 and CHI3L1.
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Jo Y, Lee JH, Cho ES, Lee HS, Shin SJ, Park EJ, Baik SH, Lee KY, Kang J. Clinical Significance of Early Carcinoembryonic Antigen Change in Patients With Nonmetastatic Colorectal Cancer. Front Oncol 2022; 12:739614. [PMID: 35615159 PMCID: PMC9124957 DOI: 10.3389/fonc.2022.739614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 04/15/2022] [Indexed: 12/28/2022] Open
Abstract
Background This study aimed to evaluate the prognostic significance of preoperative, postoperative, and trajectory changes in carcinoembryonic antigen (CEA) levels in patients with colorectal cancer (CRC). Methods This retrospective study included patients who underwent surgical resection for nonmetastatic CRC. The optimal cutoff values of preoperative CEA (CEA-pre), early postoperative CEA (CEA-post), and CEA level change (CEA-delta) were determined to maximize the differences in overall survival (OS) among groups. The patients were divided into three groups according to CEA-trend: normal, low CEA-pre; normalized, high CEA-pre/low CEA-post; elevated, high CEA-pre/high CEA-post. The integrated area under the curve (iAUC) was used to compare the discriminatory power of all variables. Results A total of 1019 patients diagnosed with stage I–III CRC were enrolled. The optimal cutoff values of CEA level were determined as 2.3 ng/mL for CEA-pre, 2.3 ng/mL for CEA-post, and -0.93 ng/mL for CEA-delta. Although subgroup dichotomization showed that CEA-pre, CEA-post, CEA-delta, and CEA-trend were all associated with OS in univariate analysis, CEA-trend was the only independent prognostic factor in multivariate analysis. The iAUC of CEA-trend was superior to that of CEA-pre, CEA-post, and CEA-delta. Compared with the normal group, the normalized group showed worse OS (p=.0007) in stage II patients but similar OS (p=.067) in stage III patients. Conclusion The optimal cutoff value of CEA level in the preoperative and postoperative periods was determined to be 2.3 ng/mL, and the combination of CEA-pre and CEA-post showed better prognostic stratification. However, its prognostic significance may differ depending on the CRC stage.
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Affiliation(s)
- Younghoo Jo
- Yonsei University College of Medicine, Seoul, South Korea
| | - Jae-Hoon Lee
- Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun-Suk Cho
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea
| | - Su-Jin Shin
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun Jung Park
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Hyuk Baik
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Kang Young Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jeonghyun Kang
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Jeonghyun Kang,
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Colorectal Cancer Diagnosis: The Obstacles We Face in Determining a Non-Invasive Test and Current Advances in Biomarker Detection. Cancers (Basel) 2022; 14:cancers14081889. [PMID: 35454792 PMCID: PMC9029324 DOI: 10.3390/cancers14081889] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/04/2022] [Accepted: 04/06/2022] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Colorectal cancer (CRC) is one of the most common cancers in the western world. CRC originates from precursor adenomatous polyps, which may over time develop into cancer. Endoscopic evaluation remains the gold-standard investigation for the disease. In the absence of molecular tools for early detection, the removal of neoplastic adenomas via polypectomy remains an important measure to prevent dysplastic adenomas from evolving into invasive carcinoma. Colonoscopy is an intrusive procedure that provides an uncomfortable experience for patients. Kits for testing for the presence of blood hemoglobin in the stool are now widely used, and DNA methylation-based detection kits have been approved in the USA for testing the stool and plasma, but few other molecular biomarkers have found their way into medical practice. This review summarizes current trends in the detection and screening of CRC and provides a definitive review of emerging molecular biomarkers for CRC. Abstract Globally, colorectal cancer (CRC) is the third most common cancer, with 1.4 million new cases and over 700,000 deaths per annum. Despite being one of the most common cancers, few molecular approaches to detect CRC exist. Carcinoembryonic antigen (CEA) is a known serum biomarker that is used in CRC for monitoring disease recurrence or response to treatment. However, it can also be raised in multiple benign conditions, thus having no value in early detection or screening for CRC. Molecular biomarkers play an ever-increasing role in the diagnosis, prognosis, and outcome prediction of disease, however, only a limited number of biomarkers are available and none are suitable for early detection and screening of CRC. A PCR-based Epi proColon® blood plasma test for the detection of methylated SEPT9 has been approved by the USFDA for CRC screening in the USA, alongside a stool test for methylated DNA from CRC cells. However, these are reserved for patients who decline traditional screening methods. There remains an urgent need for the development of non-invasive molecular biomarkers that are highly specific and sensitive to CRC and that can be used routinely for early detection and screening. A molecular approach to the discovery of CRC biomarkers focuses on the analysis of the transcriptome of cancer cells to identify differentially expressed genes and proteins. A systematic search of the literature yielded over 100 differentially expressed CRC molecular markers, of which the vast majority are overexpressed in CRC. In terms of function, they largely belong to biological pathways involved in cell division, regulation of gene expression, or cell proliferation, to name a few. This review evaluates the current methods used for CRC screening, current availability of biomarkers, and new advances within the field of biomarker detection for screening and early diagnosis of CRC.
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Long C, Xu QB, Ding L, Huang LJ, Ji Y. Circular RNAs as Diagnostic and Prognostic Indicators of Colorectal Cancer: A Pooled Analysis of Individual Studies. Pathol Oncol Res 2022; 28:1610037. [PMID: 35369570 PMCID: PMC8967936 DOI: 10.3389/pore.2022.1610037] [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] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 02/08/2022] [Indexed: 11/17/2022]
Abstract
Background: Circular RNAs (circRNAs) have proven as a special subset of endogenous RNAs that are implicated in the tumorigenesis of various cancers. This study sought to evaluate the role of circRNAs in the diagnosis and prognosis of colorectal cancer (CRC). Methods: The online databases were searched for collecting relevant studies on circRNAs as diagnostic and prognostic biomarkers of CRC. Two researchers independently screened literature, extracted data, and evaluated the bias and risks of included studies. The diagnostic and prognostic indicators were merged and analyzed using STATA 12.0 software, and sources of heterogeneity were traced by the sensitivity analysis and the meta-regression test. Results: A total of 29 articles representing 2639 CRC patients were included. The pooled sensitivity, specificity, and area under the curve (AUC) of circRNAs in differentiating CRC from non-tumor control were 0.75 (95% CI: 0.69-0.80) and 0.74 (95% CI: 0.69-0.78) and 0.81, respectively. The survival analysis showed that up-regulations of up-regulated circRNAs were significantly related to dismal survival in CRC patients (HR = 2.38, p < 0.001). A stratified analysis showed that the comprehensive diagnostic value of up-regualted circRNAs in CRC was higher than that of down-regualted circRNAs (AUC: 0.83 vs. 0.77; Z test, p < 0.05). The efficacy of tissue-derived circRNAs in the diagnosis of CRC was equal to that of plasma/serum-derived ones (AUC: 0.81 vs. 0.82; Z test, p > 0.05). Conclusion: Abnormally expressed circRNAs as auxiliary biomarkers present underlying value in the diagnosis and prognosis prediction of CRC.
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Affiliation(s)
- Cong Long
- Department of Clinical Laboratory, Jingjiang People’s Hospital, Taizhou, China
| | - Qiu-bo Xu
- Department of Clinical Laboratory, Jingjiang People’s Hospital, Taizhou, China
| | - Li Ding
- Department of Clinical Laboratory, Jingjiang People’s Hospital, Taizhou, China
| | - Li-juan Huang
- Department of Clinical Laboratory, Jingjiang People’s Hospital, Taizhou, China
| | - Yong Ji
- Department of General Surgery, Jingjiang People’s Hospital, Taizhou, China
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Xiao R, Liu C, Zhang B, Ma L. Tumor-Educated Platelets as a Promising Biomarker for Blood-Based Detection of Renal Cell Carcinoma. Front Oncol 2022; 12:844520. [PMID: 35321426 PMCID: PMC8936192 DOI: 10.3389/fonc.2022.844520] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 02/07/2022] [Indexed: 12/13/2022] Open
Abstract
Purpose Tumor-educated platelets (TEPs) are a promising liquid biopsy in many cancers. However, their role in renal cell carcinoma (RCC) is unknown. Thus, this study explored the diagnostic value of TEPs in RCC patients. Methods Platelets were prospectively collected from 24 RCC patients and 25 controls. RNA-seq was performed to identify the differentially expressed genes (DEGs) between RCC patients and controls. Besides, RNA-seq data of pan-cancer TEPs were downloaded and randomly divided into training and validation sets. A pan-cancer TEP model was developed in the training set using the support vector machine (SVM) and validated in the validation set and our RCC dataset. Finally, an RCC-based TEP model was developed and optimized through the SVM algorithms and recursive feature elimination (RFE) method. Result Two hundred three DEGs, 64 (31.5%) upregulated and 139 (68.5%) downregulated, were detected in the platelets of RCC patients compared with controls. The pan-cancer TEP model had a high accuracy in detecting cancer in the internal validation (training set, accuracy 98.8%, AUC: 0.999; validation set, accuracy 95.4%, AUC: 0.972; different tumor subtypes, accuracy 86.6%–96.1%, AUC: 0.952–1.000). However, the pan-cancer TEP model in the external validation had a scarce diagnostic value in RCC patients (accuracy 48.7%, AUC: 0.615). Therefore, to develop the RCC-based TEP model, the gene biomarkers mostly contributing to the model were selected using the RFE method. The RCC-based TEP model containing 68 gene biomarkers reached a diagnostic accuracy of 100% (AUC: 1.000) in the training set, 88.9% (AUC: 0.963) in the validation set, and 95.9% (AUC: 0.988) in the overall cohort. Conclusion TEPs could function as a minimally invasive blood biomarker in the detection of RCC.
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Affiliation(s)
- Ruotao Xiao
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Cheng Liu
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Bo Zhang
- Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Lulin Ma
- Department of Urology, Peking University Third Hospital, Beijing, China
- *Correspondence: Lulin Ma,
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Thomas AE, Kazi M, Bankar S, Mokal S, Agarwal A, Rangarajan V, Desouza A, Saklani A. Elevated CEA with negative PET scan on surveillance of colorectal cancers-a role of CEA kinetics. Langenbecks Arch Surg 2022; 407:769-778. [PMID: 34654962 DOI: 10.1007/s00423-021-02352-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 10/06/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The management of patients with elevated CEA after curative treatment of colorectal cancers without structural disease is uncertain. The aim was to study the clinical risk factors, CEA thresholds, and kinetics that could predict relapses. METHODS Retrospective study of colorectal cancers patients that were detected to have an elevated CEA (> 5 ng/ml on 2 separate occasions) and normal clinical exam, colonoscopy, and positron emission tomography (PET). Receiver operating characteristic (ROC) curves were generated to determine the optimal cutoff for absolute CEA values and proportional rise that could predict recurrences. RESULTS 162 patients were followed for a median of 42 months. 32 patients (19.7%) relapsed of which 11 (34.4%) had a peritoneal disease. Besides known clinical risk factors, higher CEA at the time of negative PET and rising CEA trend predicted disease recurrence on multivariate logistic regression. CEA threshold of 10.05 ng/ml provided a sensitivity/specificity of 53%/86.2%, while CEA velocity of 1.36 ng/ml over 3 months presented a sensitivity/specificity of 80%/70.6% for subsequent relapse. CONCLUSIONS The discriminatory value of CEA kinetics was more than that of a single absolute value. An algorithm for managing these patients based on clinical risk factors, absolute CEA value, and its kinetics is suggested.
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Affiliation(s)
- Anand Ebin Thomas
- Department of Surgical Oncology, Malabar Cancer Centre, Kerala, 670103, India
| | - Mufaddal Kazi
- Department of Colorectal Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Dr Ernest Borges Marg, Parel, Mumbai, Maharashtra, 400012, India
| | - Sanket Bankar
- Dr. D.Y. Patil Medical College and Research Institute, Pimpri, Pune and Dr. D.Y. Patil Vidyapeeth, Pune , India
| | - Smruti Mokal
- Department of Clinical Research Secretariat, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, 400012, India
| | - Archi Agarwal
- Department of Nuclear Medicine, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, 400012, India
| | - Ventakesh Rangarajan
- Department of Nuclear Medicine, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, 400012, India
| | - Ashwin Desouza
- Department of Colorectal Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Dr Ernest Borges Marg, Parel, Mumbai, Maharashtra, 400012, India
| | - Avanish Saklani
- Department of Colorectal Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Dr Ernest Borges Marg, Parel, Mumbai, Maharashtra, 400012, India.
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Clinical Validity of Circulating Tumor DNA as Prognostic and Predictive Marker for Personalized Colorectal Cancer Patient Management. Cancers (Basel) 2022; 14:cancers14030851. [PMID: 35159118 PMCID: PMC8834623 DOI: 10.3390/cancers14030851] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 01/21/2022] [Accepted: 02/07/2022] [Indexed: 12/30/2022] Open
Abstract
Simple Summary CtDNA analysis is a promising tool in liquid biopsy for the detection of tumor recurrence and progression, and is increasingly adopted into clinical practice. Still, guidelines for the accurate clinical interpretation of ctDNA analysis results are largely lacking, especially for tumor mutant variants detected at very low frequencies. Here, we show that cutoff determination for the detection and quantification of low-frequency mutant variants enables the accurate prediction of residual disease, tumor recurrence and progression, even before clinical evidence. CtDNA analysis using these cutoffs outperformed cfDNA and CEA level measurements. With these findings, we highlight the need to thoroughly validate each liquid biopsy assay and define the assay-specific limit of blanks (LOB) and limit of quantifications (LOQ) of BRAF p.V600E and KRAS p.G12/p.G13 assays for clinical interpretation. Our approach enables accurate clinical interpretation to support clinical decision making. Abstract Circulating tumor DNA (ctDNA) is a promising liquid biopsy (LB) marker to support clinical decisions in precision medicine. For implementation into routine clinical practice, clinicians need precise ctDNA level cutoffs for reporting residual disease and monitoring tumor burden changes during therapy. We clinically validated the limit of blank (LOB) and the limit of quantification (LOQ) of assays for the clinically most relevant somatic variants BRAF p.V600E and KRAS p.G12/p.G13 in colorectal cancer (CRC) in a study cohort encompassing a total of 212 plasma samples. We prove that residual disease detection using the LOB as a clinically verified cutoff for ctDNA positivity is in concordance with clinical evidence of metastasis or recurrence. We further show that tumor burden changes during chemotherapy and the course of disease are correctly predicted using the LOQ as a cutoff for quantitative ctDNA changes. The high potential of LB using ctDNA for accurately predicting the course of disease was proven by direct comparison to the routinely used carcinoembryonic antigen (CEA) as well as the circulating free DNA (cfDNA) concentration. Our results show that LB using validated ctDNA assays outperforms CEA and cfDNA for residual disease detection and the prediction of tumor burden changes.
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Aires F, Rodrigues D, Lamas MP, Herdeiro MT, Figueiras A, Oliveira MJ, Marques M, Pinto AT. C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study. Cancers (Basel) 2022; 14:491. [PMID: 35158759 PMCID: PMC8833484 DOI: 10.3390/cancers14030491] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 01/05/2022] [Accepted: 01/14/2022] [Indexed: 01/27/2023] Open
Abstract
The standard of care for the treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery, but complete response rates are reduced. To find predictive biomarkers of response to therapy, we conducted a retrospective study evaluating blood biomarkers before nCRT. Hemoglobin (Hg), C-reactive protein (CRP), platelets, carcinoembryonic antigen, carbohydrate antigen 19.9 levels, and neutrophil/lymphocyte ratio were obtained from 171 rectal cancer patients before nCRT. Patients were classified as responders (Ryan 0-1; ycT0N0), 59.6% (n = 102), or nonresponders (Ryan 2-3), 40.3% (n = 69), in accordance with the Ryan classification. A logistic regression using prognostic pretreatment factors identified CRP ≤ 3.5 (OR = 0.05; 95%CI: 0.01-0.21) as a strong independent predictor of response to treatment. Multivariate analysis showed that CRP was an independent predictor of disease-free survival (DFS) (HR = 5.48; 95%CI: 1.54-19.48) and overall survival (HR = 6.10; 95%CI 1.27-29.33) in patients treated with nCRT. Platelets were an independent predictor of DFS (HR = 3.068; 95%CI: 1.29-7.30) and OS (HR= 4.65; 95%CI: 1.66-13.05) and Hg was revealed to be an independent predictor of DFS (HR = 0.37; 95%CI: 0.15-0.90) in rectal cancer patients treated with nCRT. The lower expression of CRP is independently associated with an improved response to nCRT, DFS, and OS.
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Affiliation(s)
- Fátima Aires
- Radiotherapy Department of Centro Hospitalar Universitário de São João (CHUSJ), 4200-319 Porto, Portugal; (D.R.); (M.M.)
| | - Darlene Rodrigues
- Radiotherapy Department of Centro Hospitalar Universitário de São João (CHUSJ), 4200-319 Porto, Portugal; (D.R.); (M.M.)
- ICBAS–Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal;
- CINTESIS–Center for Health Technology and Services Research, University of Porto, 4200-450 Porto, Portugal
| | - María Piñeiro Lamas
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiology and Public Health–CIBERESP), 15706 Santiago de Compostela, Spain; (M.P.L.); (A.F.)
- Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, 15706 Santiago de Compostela, Spain
| | - Maria Teresa Herdeiro
- Department of Medical Sciences, Institute of Biomedicine–iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; (M.T.H.); (A.T.P.)
| | - Adolfo Figueiras
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiology and Public Health–CIBERESP), 15706 Santiago de Compostela, Spain; (M.P.L.); (A.F.)
- Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, 15706 Santiago de Compostela, Spain
- Faculty of Medicine, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain
| | - Maria José Oliveira
- ICBAS–Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal;
- i3S–Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
- INEB–Instituto de Engenharia Biomédica, University of Porto, 4200-135 Porto, Portugal
| | - Margarida Marques
- Radiotherapy Department of Centro Hospitalar Universitário de São João (CHUSJ), 4200-319 Porto, Portugal; (D.R.); (M.M.)
| | - Ana Teresa Pinto
- Department of Medical Sciences, Institute of Biomedicine–iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; (M.T.H.); (A.T.P.)
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Eskander NS, Mansour L, Abdelaal A, Saad E, Mohamed D. Circulating Cell Free DNA Integrity Index as a Biomarker for Response to Chemotherapy in Patients with Metastatic Colorectal Carcinoma. Asian Pac J Cancer Prev 2022; 23:339-348. [PMID: 35092403 PMCID: PMC9258663 DOI: 10.31557/apjcp.2022.23.1.339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 01/18/2022] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE Assessing plasma Cell Free DNA (cfDNA) integrity index as a biomarker for response prediction and early response evaluation in mCRC patients receiving chemotherapy, in comparison to Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9), to be used as an additional tool to computed tomography (CT). METHODS CEA, CA19-9, cfDNA concentration and cfDNA integrity index (ALU 247/115) measurements were conducted on 86 subjects divided into 43 healthy volunteers and 43 mCRC patients, before starting chemotherapy and then after 6-12 weeks of therapy initiation (3-4 cycles FOLFOX) at first response assessment. Plasma cfDNA integrity index was calculated as the ratio of long to short DNA fragments (ALU 247/115) amplified and detected by real-time PCR. Serum CEA and CA19-9 were measured by chemiluminescent immunometric assay. RESULTS Baseline cfDNA integrity index was statistically significantly different between responders and non-responders (p=0.03). It was found that at cut off 0.608, sensitivity was 73.7%, specificity was 66.7% and diagnostic accuracy=69.77%. Markers with statistical significant difference between responders and non-responders after chemotherapy were CEA % change (p=0.035), CA19-9 (p=0.024), cfDNA integrity index (p=0.035) and cfDNA integrity index % change (p<0.001). Among these markers, cfDNA integrity index % change had the best sensitivity (84.2%), specificity (95.2%) and diagnostic accuracy (90.7%) at cut off -17.827%. CONCLUSION Baseline cfDNA integrity index can be used as a potential marker to predict response to chemotherapy. cfDNA integrity index (ALU 247/115) % change rather than its absolute value is superior to CEA, CA19-9, cfDNA concentration and their % changes in early assessment of response to chemotherapy.
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Affiliation(s)
- Nancy Samir Eskander
- Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Lamia Mansour
- Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Amaal Abdelaal
- Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Ehab Saad
- Department of Cinical Oncology and Nuclear Medicine, Cairo University, Egypt.
| | - Doaa Mohamed
- Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
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Eigeliene N, Saarenheimo J, Wichmann V, Österlund P, Jekunen A. Metastatic Rectal Carcinoma with Long-Term Remission due to Modern Multimodality Treatment. Case Rep Oncol 2021; 14:1475-1482. [PMID: 34899239 PMCID: PMC8613627 DOI: 10.1159/000519044] [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: 05/20/2021] [Accepted: 08/14/2021] [Indexed: 12/24/2022] Open
Abstract
In the era of personalized medicine, systemic treatment with chemotherapy in combination with targeted drugs, tailored according to RAS and BRAF status, has improved the survival of patients with metastatic colorectal cancer (mCRC), but curative resection of metastases provides the only chance of cure. Here, we present a 40-year-old male with rectal adenocarcinoma and multiple bilateral synchronous liver metastases who has achieved long-term remission with multimodal treatment without resection of all metastatic lesions. This case emphasizes the need of repeated multidisciplinary team assessments and change of treatment intent if extraordinary responses are seen. The initial therapy consisted of short-course radiotherapy and surgery of the primary tumor followed by oxaliplatin-based combination chemotherapy and panitumumab with disease control intent. A complete radiologic response in >20 liver metastases in segments II–VIII was obtained. A biopsy-verified relapse of 3 liver metastases occurred at 9 months of treatment pause. Subsequently, major liver resection of 8 lesions was performed (4 with adenocarcinoma and 4 with cicatrix showing the challenge of disappearing lesions), followed by 6 months of adjuvant-like therapy. No relapse in MRI, PET, or CT has been noted since liver resection 6 years ago. Comprehensive genomic profiling of the primary tumor and liver metastases had similar driver mutations representing a low level of gene alteration and low diversity, possibly explaining the exceptional treatment response.
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Affiliation(s)
- Natalja Eigeliene
- Department of Oncology, Vaasa Central Hospital, Vaasa, Finland.,University of Turku, Department of Oncology and Radiotherapy, Turku, Finland
| | - Jatta Saarenheimo
- Department of Oncology, Vaasa Central Hospital, Vaasa, Finland.,Department of Pathology, Vaasa Central Hospital, Vaasa, Finland
| | - Viktor Wichmann
- Department of Oncology, Vaasa Central Hospital, Vaasa, Finland.,University of Turku, Department of Oncology and Radiotherapy, Turku, Finland
| | - Pia Österlund
- Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland.,Department of Oncology & Pathology, Karolinska Institutet and Karolinska Comprehensive, Cancer Centre, Stockholm, Sweden
| | - Antti Jekunen
- Department of Oncology, Vaasa Central Hospital, Vaasa, Finland.,University of Turku, Department of Oncology and Radiotherapy, Turku, Finland
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Loosen SH, Roderburg C, Alizai PH, Roeth AA, Schmitz SM, Vucur M, Luedde M, Schöler D, Paffenholz P, Tacke F, Trautwein C, Luedde T, Neumann UP, Ulmer TF. Comparative Analysis of Circulating Biomarkers for Patients Undergoing Resection of Colorectal Liver Metastases. Diagnostics (Basel) 2021; 11:diagnostics11111999. [PMID: 34829346 PMCID: PMC8622404 DOI: 10.3390/diagnostics11111999] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/07/2021] [Accepted: 10/25/2021] [Indexed: 12/22/2022] Open
Abstract
Surgical tumor resection has evolved as a potentially curative therapy for patients with resectable colorectal liver metastases (CRLM). However, disease recurrence is common and the available preoperative stratification strategies are often imprecise to identify the ideal candidates for surgical treatment, resulting in a postoperative 5-year survival rate below 50%. Data on the prognostic value of CEA, CA19-9 and other common laboratory parameters after CRLM resection are scarce and partly inconclusive. Here, we analyzed the prognostic potential of circulating CEA and CA19-9 in comparison to other standard laboratory markers in resectable CRLM patients. Serum levels of tumor markers and other laboratory parameters were analyzed in 125 patients with CRLM undergoing tumor resection at a tertiary referral center. Results were correlated with clinical data and outcome. Both tumor markers were significantly elevated in CRLM patients compared to healthy controls. Interestingly, elevated levels of CEA, CA19-9 and C-reactive protein (CRP) were associated with an unfavorable prognosis after CRLM resection in Kaplan-Meier curve analysis. However, only CEA and not CA19-9 or CRP serum levels were an independent prognostic marker in multivariate Cox regression analysis. Our data demonstrate that circulating levels of CEA rather than CA19-9 might be a valuable addition to the existing preoperative stratification algorithms to identify patients with a poor prognosis after CRLM resection.
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Affiliation(s)
- Sven H. Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (C.R.); (M.V.); (D.S.); (T.L.)
- Correspondence:
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (C.R.); (M.V.); (D.S.); (T.L.)
| | - Patrick H. Alizai
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany; (P.H.A.); (A.A.R.); (S.M.S.); (U.P.N.); (T.F.U.)
| | - Anjali A. Roeth
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany; (P.H.A.); (A.A.R.); (S.M.S.); (U.P.N.); (T.F.U.)
| | - Sophia M. Schmitz
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany; (P.H.A.); (A.A.R.); (S.M.S.); (U.P.N.); (T.F.U.)
| | - Mihael Vucur
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (C.R.); (M.V.); (D.S.); (T.L.)
| | - Mark Luedde
- KGP Bremerhaven, Postbrookstraße 105, 27574 Bremerhaven, Germany;
| | - David Schöler
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (C.R.); (M.V.); (D.S.); (T.L.)
| | - Pia Paffenholz
- Department of Urology, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany;
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;
| | - Christian Trautwein
- Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany;
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (C.R.); (M.V.); (D.S.); (T.L.)
| | - Ulf P. Neumann
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany; (P.H.A.); (A.A.R.); (S.M.S.); (U.P.N.); (T.F.U.)
- Department of Surgery, Maastricht University Medical Centre (MUMC), 5800 Maastricht, The Netherlands
| | - Tom F. Ulmer
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany; (P.H.A.); (A.A.R.); (S.M.S.); (U.P.N.); (T.F.U.)
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Wang L, Zhong X, Lin H, Shao L, Chen G, Wu J. The Correlation Between Survival Benefit of Preoperative Radiotherapy and Pretreatment Carcinoembryonic Antigen Level in Locally Advanced Rectal Cancer. Front Oncol 2021; 11:735882. [PMID: 34692510 PMCID: PMC8529282 DOI: 10.3389/fonc.2021.735882] [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: 07/15/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
Background Preoperative radiotherapy followed by radical surgery is the standard treatment for locally advanced rectal cancer; however, its long-term survival benefit remains controversial. This study aimed to determine the relationship between pretreatment carcinoembryonic antigen (CEA) levels and the long-term prognosis of preoperative radiotherapy in locally advanced rectal cancer (LARC) patients. Methods Data of LARC patients who underwent surgery between 2011 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients were accordingly divided into surgery (S) group and radiotherapy followed by surgery (RT+S) group. The primary outcomes were cancer-specific survival (CSS) and cancer-specific mortality (CSM). CSS was evaluated using Kaplan-Meier analysis, while CSM was evaluated using a competitive risk model. Subgroup analysis was also conducted, which was stratified by pretreatment CEA levels. Results A total of 2,760 patients were eligible for this study, including 350 (12.7%) patients in the S group and 2,410 (87.3%) in the RT+S group. There were no significant differences in the CSS and CSM rates at 1, 3, and 4 years between the S and RT+S groups before and after PSM (all p > 0.05). Pretreatment CEA levels were independently associated with CSS and CSM after adjusting for age, sex, stage, pathological factors, and treatment factors (all p < 0.05). Subgroup analysis showed that preoperative radiotherapy would benefit patients with elevated CEA in terms of CSS and CSM (both p < 0.05) but not those patients with normal CEA (both p > 0.05). Further analysis showed that preoperative radiotherapy was an independent protective factor for CSS and CSM in patients with elevated CEA levels (both p < 0.05). Conclusions Pretreatment CEA level may be considered a potential biomarker to screen LACR patients who would benefit from preoperative radiotherapy in terms of long-term prognosis.
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Affiliation(s)
- Lei Wang
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Xiaohong Zhong
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Huaqin Lin
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Lingdong Shao
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Gang Chen
- Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
| | - Junxin Wu
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
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Li X, Xiong Z, Xie M, Huang Q, Jin L, Yin S, Chen S, Lan P, Lian L. Prognostic value of the ratio of carcinoembryonic antigen concentration to maximum tumor diameter in patients with stage II colorectal cancer. J Gastrointest Oncol 2021; 12:1470-1481. [PMID: 34532103 DOI: 10.21037/jgo-21-61] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 06/08/2021] [Indexed: 12/16/2022] Open
Abstract
Background Recently, a study from our center indicated that the ratio of preoperative carcinoembryonic antigen (CEA) concentration to maximum tumor diameter (DMAX) may be a prognostic marker for patients with rectal cancer. Therefore, the study aimed to evaluate whether this ratio (CEA/DMAX) has prognostic value for patients with stage II colorectal cancer (CRC). Methods A prospectively maintained database was searched for patients with pathologically confirmed stage II CRC who underwent surgery between January 2010 and March 2019. Patients were stratified according to the mean CEA/DMAX value into low and high CEA/DMAX groups. Kaplan-Meier, univariable, and multivariable Cox regression analyses were used to evaluate whether the CEA/DMAX could predict overall survival (OS) and disease-free survival (DFS). Nomograms were constructed in terms of the results of multivariable Cox regression analyses. Results The study included 2,499 patients with stage II CRC. The mean CEA/DMAX value was 2.33 (ng/mL per cm). Kaplan-Meier analyses revealed that, relative to the low CEA/DMAX group, the high CEA/DMAX group had significantly poorer OS (67.31% vs. 85.02%, P<0.001) and DFS (61.41% vs. 77.10%, P<0.001). The multivariable Cox regression analysis revealed that CEA/DMAX independently predicted OS (hazard ratio: 2.58, 95% confidence interval: 1.51-4.38, P<0.001) and DFS (hazard ratio: 1.97, 95% confidence interval: 1.38-2.83, P<0.001). Two simple-to-use nomograms comprising CEA/DMAX, age, T stage, and lymphovascular invasion were developed to predict 1-, 3-, and 5-year rates of OS and DFS among patients with stage II CRC. The nomograms had good performance based on the concordance index, receiver operating characteristic (ROC) curve analysis, and calibration curves. Subgroup analyses further confirmed that a high CEA/DMAX was associated with poor OS and DFS among patients with stage II colon cancer and among patients with stage II rectal cancer (both P<0.05). Conclusions Among patients with stage II CRC, a high CEA/DMAX independently predicted poor OS and DFS, and the predictive abilities were also observed in subgroup analyses of patients with stage II colon cancer or rectal cancer. Furthermore, we developed two nomograms that had good accuracy for predicting the prognosis of stage II CRC.
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Affiliation(s)
- Xianzhe Li
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhizhong Xiong
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minghao Xie
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qunsheng Huang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Longyang Jin
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shi Yin
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuanggang Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ping Lan
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lei Lian
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Yuan B, Ma B, Yu J, Meng Q, Du T, Li H, Zhu Y, Sun Z, Ma S, Song C. Fecal Bacteria as Non-Invasive Biomarkers for Colorectal Adenocarcinoma. Front Oncol 2021; 11:664321. [PMID: 34447694 PMCID: PMC8383742 DOI: 10.3389/fonc.2021.664321] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 06/07/2021] [Indexed: 12/14/2022] Open
Abstract
Colorectal adenocarcinoma (CRC) ranks one of the five most lethal malignant tumors both in China and worldwide. Early diagnosis and treatment of CRC could substantially increase the survival rate. Emerging evidence has revealed the importance of gut microbiome on CRC, thus fecal microbial community could be termed as a potential screen for non-invasive diagnosis. Importantly, few numbers of bacteria genus as non-invasive biomarkers with high sensitivity and specificity causing less cost would be benefitted more in clinical compared with the whole microbial community analysis. Here we analyzed the gut microbiome between CRC patients and healthy people using 16s rRNA sequencing showing the divergence of microbial composition between case and control. Furthermore, ExtraTrees classifier was performed for the classification of CRC gut microbiome and heathy control, and 13 bacteria were screened as biomarkers for CRC. In addition, 13 biomarkers including 12 bacteria genera and FOBT showed an outstanding sensitivity and specificity for discrimination of CRC patients from healthy controls. This method could be used as a non-invasive method for CRC early diagnosis.
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Affiliation(s)
- Biao Yuan
- Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University of Medicine, Shanghai, China
| | - Bin Ma
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Jing Yu
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China.,ECNU-PERSONAL Joint Laboratory of Genetic Detection and Application, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Qingkai Meng
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Tao Du
- Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University of Medicine, Shanghai, China
| | - Hongyi Li
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Yueyan Zhu
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Zikui Sun
- Research and Development Department, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China.,ECNU-PERSONAL Joint Laboratory of Genetic Detection and Application, Shanghai Personal Biotechnology Co., Ltd, Shanghai, China
| | - Siping Ma
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Chun Song
- Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University of Medicine, Shanghai, China
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Carcinoembryonic Antigen Increase in a Patient with Colon Cancer Who Have Achieved Complete Remission and Negative 18F-FDG PET/CT: Don't Forget the Thyroid! ACTA ACUST UNITED AC 2021; 28:2987-2992. [PMID: 34436027 PMCID: PMC8395414 DOI: 10.3390/curroncol28040261] [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: 06/18/2021] [Revised: 07/27/2021] [Accepted: 08/04/2021] [Indexed: 11/30/2022]
Abstract
Serum carcinoembryonic antigen (CEA) is a tumor marker especially used to follow a patient with colorectal cancer. However, it is non-specific and could be increased in several cancers and some benign conditions. We report the case of a 70-year-old man followed since 2014 for a left colon adenocarcinoma with the persistence of an increased CEA. There was no evidence of recurrence, but a right lobar thyroid nodule without a significantly increased uptake was incidentally discovered on the CT scan of 18F-fluorodeoxyglucose (18F-FDG) PET/CT. We suspected a medullary thyroid carcinoma (MTC) explaining the persistent elevation of CEA. Plasma calcitonin levels were 47 ng/L (N < 10). Fine needle aspiration cytology found atypia of undetermined significance and the patient was reluctant to undergo surgery without any further exploration. We performed a 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT preoperatively which revealed a punctiform focus of the right thyroid lobe corresponding to a pT1aN1aMxR0 medullary thyroid carcinoma, histopathologically confirmed. This case highlights that despite the potential usefulness of 18F-FDG PET/CT in case of an unknown source of elevated CEA this imaging may be falsely negative as in the case of MTC and should lead to further explorations.
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