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Chen B, Fan H, Pang X, Shen Z, Gao R, Wang H, Yu Z, Li T, Li M, Tang Y, Liang X. Single-cell and spatial transcriptomics reveals an anti-tumor neutrophil subgroup in microwave thermochemotherapy-treated lip cancer. Int J Oral Sci 2025; 17:40. [PMID: 40360503 PMCID: PMC12075663 DOI: 10.1038/s41368-025-00366-8] [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: 03/03/2024] [Revised: 12/29/2024] [Accepted: 03/25/2025] [Indexed: 05/15/2025] Open
Abstract
Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA+ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
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Affiliation(s)
- Bingjun Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Huayang Fan
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xin Pang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zeliang Shen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Rui Gao
- University of Electronic Science and Technology of China, Chengdu, China
| | - Haofan Wang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhenwei Yu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Tianjiao Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Mao Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yaling Tang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Xinhua Liang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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Sanghvi G, R R, Kashyap A, Sabarivani A, Ray S, Bhakuni PN. Identifying the function of kinesin superfamily proteins in gastric cancer: Implications for signal transduction, clinical significance, and potential therapeutic approaches. Clin Res Hepatol Gastroenterol 2025; 49:102571. [PMID: 40064398 DOI: 10.1016/j.clinre.2025.102571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/06/2025] [Accepted: 03/08/2025] [Indexed: 03/16/2025]
Abstract
Gastric cancer (GC), a leading cause of cancer-related mortality, poses a significant global health challenge. Given its complex etiology, understanding the molecular pathways driving GC progression is crucial for developing innovative therapeutic strategies. Among the diverse proteins involved in cellular transport and mitotic regulation, kinesin superfamily proteins (KIFs) have emerged as key players in tumor biology. These motor proteins mediate intracellular transport along microtubules and are essential for processes such as cell division, signaling, and organelle distribution. Evidence indicates that specific KIFs are dysregulated in GC, potentially driving cancer cell proliferation, metastasis, and chemoresistance. Moreover, aberrant KIF expression has been associated with poorer prognoses, highlighting their potential as biomarkers for early diagnosis and therapeutic intervention. This review explores the roles of KIFs in GC and assesses their implications for research and clinical applications. By elucidating the significance of KIFs in GC, this discussion aims to inspire novel insights in cancer biology and advance targeted therapeutic strategies.
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Affiliation(s)
- Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat 360003, India
| | - Roopashree R
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Aditya Kashyap
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab 140401, India
| | - A Sabarivani
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Subhashree Ray
- Department of Biochemistry, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha 751003, India
| | - Pushpa Negi Bhakuni
- Department of Allied Science, Graphic Era Hill University, Bhimtal, Uttarakhand 248002, India; Graphic Era Deemed to be University, Dehradun, Uttarakhand, India.
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Cheng G, Zhou Z, Li S, Peng F, Yang S, Ren C. Machine learning-derived prognostic signature integrating programmed cell death and mitochondrial function in renal clear cell carcinoma: identification of PIF1 as a novel target. Cancer Immunol Immunother 2025; 74:113. [PMID: 39998680 PMCID: PMC11861773 DOI: 10.1007/s00262-025-03967-8] [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: 12/31/2024] [Accepted: 02/02/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND The pathogenesis and progression of renal cell carcinoma (RCC) involve complex programmed cell death (PCD) processes. As the powerhouse of the cell, mitochondria can influence cell death mechanisms. However, the prognostic significance of the interplay between mitochondrial function (MF) and PCD remains unclear. METHODS We collected sets of genes related to PCD and MF. Using a powerful machine learning algorithm framework, we investigated the relationship between MF and PCD in different cohorts of patients and developed a machine learning-derived prognostic signature (mpMLDPS) related to MF and PCD. Finally, the most appropriate prognostic markers for RCC were screened by survival analysis and clinical correlation analysis, and the effects on renal cancer cells were analysed in vitro. RESULTS mpMLDPS was significantly correlated with the prognosis of RCC patients, and the prognosis was worse in the high mpMLDPS group, and this result was also validated in external independent cohorts. There were associations between mpMLDPS and immune checkpoints, tumour microenvironment, somatic mutations, and drug sensitivity. Finally, a novel RCC prognostic marker PIF1 was identified in model genes. The knockdown of PIF1 in vitro inhibited the progression of renal carcinoma cells. CONCLUSION mpMLDPS has great potential to serve as a reliable clinical signature to improve the accuracy and reliability of prognostic assessment in RCC patients, thereby choosing the appropriate therapeutic regimen in clinical practice. PIF1 is also expected to be a novel target for the clinical treatment of RCC.
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Affiliation(s)
- Guangyang Cheng
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Zhaokai Zhou
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Bladder Structure and Function Reconstruction Henan Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Shiqi Li
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Fu Peng
- Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Shuai Yang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
- Bladder Structure and Function Reconstruction Henan Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Chuanchuan Ren
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
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Liang GZ, Li XS, Hu ZH, Xu QJ, Wu F, Wu XL, Lei HK. Development and validation of a nomogram model for predicting overall survival in patients with gastric carcinoma. World J Gastrointest Oncol 2025; 17:95423. [PMID: 39958550 PMCID: PMC11755997 DOI: 10.4251/wjgo.v17.i2.95423] [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: 04/10/2024] [Revised: 10/01/2024] [Accepted: 11/06/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China, with the disease's intricate and varied characteristics further amplifying its health impact. Precise forecasting of overall survival (OS) is of paramount importance for the clinical management of individuals afflicted with this malignancy. AIM To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma. METHODS Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020. Least absolute shrinkage and selection operator, univariate, and multivariate Cox regression analyses were employed to identify independent prognostic factors. A nomogram model was developed to predict gastric cancer patient outcomes. The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves. To evaluate the clinical utility of the model, Kaplan-Meier and decision curve analyses were performed. RESULTS A total of ten independent prognostic factors were identified, including body mass index, tumor-node-metastasis (TNM) stage, radiation, chemotherapy, surgery, albumin, globulin, neutrophil count, lactate dehydrogenase, and platelet-to-lymphocyte ratio. The area under the curve (AUC) values for the 1-, 3-, and 5-year survival prediction in the training set were 0.843, 0.850, and 0.821, respectively. The AUC values were 0.864, 0.820, and 0.786 for the 1-, 3-, and 5-year survival prediction in the validation set, respectively. The model exhibited strong discriminative ability, with both the time AUC and time C-index exceeding 0.75. Compared with TNM staging, the model demonstrated superior clinical utility. Ultimately, a nomogram was developed via a web-based interface. CONCLUSION This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients, which demonstrated strong predictive ability. Based on these findings, this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.
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Affiliation(s)
- Guan-Zhong Liang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Xiao-Sheng Li
- Chongqing Cancer Multi-omics Big Data Application Engineering Research Center, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Zu-Hai Hu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Qian-Jie Xu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Fang Wu
- Research Center for Medicine and Social Development, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Xiang-Lin Wu
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Hai-Ke Lei
- The Research Center of Big Data, Chongqing University Cancer Hospital, Chongqing 400030, China
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Liu H, Zhao H, Zhou M, Zhao X, Lu Y. Neutrophils in cancer drug resistance: Roles and therapeutic opportunities. Cancer Lett 2024; 611:217417. [PMID: 39722405 DOI: 10.1016/j.canlet.2024.217417] [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: 10/07/2024] [Revised: 12/09/2024] [Accepted: 12/22/2024] [Indexed: 12/28/2024]
Abstract
The tumor microenvironment (TME) is closely associated with the therapeutic response and clinical outcome of cancer drug therapies, which mainly include immunotherapy, chemotherapy and targeted therapy. Neutrophils that infiltrate tumors, also known as tumor-associated neutrophils (TANs), constitute a primary part of the TME. However, the functional importance of TANs in cancer drug therapy has long been overlooked because of their relatively short life span. Recent studies have shown that TANs play crucial protumoral or antitumoral roles in cancer drug treatment, largely because of their diversity and plasticity. This review describes the development, heterogeneity and recruitment of neutrophils in the context of cancer and emphasizes the role and mechanisms of TANs in cancer drug resistance. Additionally, several potential neutrophil-targeted strategies are discussed.
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Affiliation(s)
- Hao Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China
| | - Hongyu Zhao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China
| | - Mingzhen Zhou
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China
| | - Xiaodi Zhao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
| | - Yuanyuan Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
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Zhao J, Chen H, Sun J. Dendritic Cell-Related Immune Marker CD1C for Predicting Prognosis and Immunotherapy Opportunities of Lung Adenocarcinoma Patients. Appl Biochem Biotechnol 2024; 196:8724-8740. [PMID: 38907868 DOI: 10.1007/s12010-024-04973-9] [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] [Accepted: 06/05/2024] [Indexed: 06/24/2024]
Abstract
Lung adenocarcinoma (LUAD) is the most frequent type of lung cancer with a high mortality rate. Here, we aim to explore novel immune-related biomarkers for LUAD patients. Datasets, mRNA expression profiles, and clinical data concerned with LUAD were obtained from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), respectively. Differential expression analysis was performed to obtain differentially expressed genes (DEGs). Based on DEGs, we conducted functional enrichment analyses. Subsequently, Kaplan‑Meier (KM) was performed to analyze survival differences among different groups. Furthermore, immune cell infiltration proportion was calculated by CIBERSORT and TIMER. The relationship between gene and immune response was analyzed using Tumor Immune System Interactions (TISIDB) database. Finally, Pearson correlation analysis was performed between CD1C and six immune checkpoints. We identified dendritic cells (DCs)-related expression profiles from four LUAD samples. DCs' immune marker CD1C in LUAD was selected by univariate Cox regression analysis. Low CD1C expression patients had a poor prognosis. A total of 332 DEGs were identified in high and low CD1C expression groups, which primarily enriched in 348 GO terms and 30 KEGG pathways. There were significant differences in the infiltration proportion of 17 immune cells between high and low CD1C expression groups. Most immunomodulators, chemokines, and chemokine receptors were positively associated with CD1C expression. Six immune checkpoints were also positively correlated with CD1C expression. DCs related immunomarker CD1C probably plays a pivotal part in prognosis and immunotherapy of LUAD via a joint analysis of single-cell and bulk sequencing data.
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Affiliation(s)
- Jing Zhao
- Department of Pulmonary and Critical Care Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, No. 166, Yulong West Road, Yancheng, 224000, Jiangsu, P.R. China
| | - Hao Chen
- Yancheng Maternal and Child Health Care Hospital, Yancheng, 224000, Jiangsu, P.R. China
| | - Jian Sun
- Department of Pulmonary and Critical Care Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, No. 166, Yulong West Road, Yancheng, 224000, Jiangsu, P.R. China.
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Yin R, Dou Z, Wang Y, Zhang Q, Guo Y, Wang Y, Chen Y, Zhang C, Li H, Jian X, Qi L, Ma W. Preoperative CECT-Based Multitask Model Predicts Peritoneal Recurrence and Disease-Free Survival in Advanced Ovarian Cancer: A Multicenter Study. Acad Radiol 2024; 31:4488-4498. [PMID: 38693025 DOI: 10.1016/j.acra.2024.04.024] [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: 01/22/2024] [Revised: 04/13/2024] [Accepted: 04/14/2024] [Indexed: 05/03/2024]
Abstract
RATIONALE AND OBJECTIVES Peritoneal recurrence is the predominant pattern of recurrence in advanced ovarian cancer (AOC) and portends a dismal prognosis. Accurate prediction of peritoneal recurrence and disease-free survival (DFS) is crucial to identify patients who might benefit from intensive treatment. We aimed to develop a predictive model for peritoneal recurrence and prognosis in AOC. METHODS In this retrospective multi-institution study of 515 patients, an end-to-end multi-task convolutional neural network (MCNN) comprising a segmentation convolutional neural network (CNN) and a classification CNN was developed and tested using preoperative CT images, and MCNN-score was generated to indicate the peritoneal recurrence and DFS status in patients with AOC. We evaluated the accuracy of the model for automatic segmentation and predict prognosis. RESULTS The MCNN achieved promising segmentation performances with a mean Dice coefficient of 84.3% (range: 78.8%-87.0%). The MCNN was able to predict peritoneal recurrence in the training (AUC 0.87; 95% CI 0.82-0.90), internal test (0.88; 0.85-0.92), and external test set (0.82; 0.78-0.86). Similarly, MCNN demonstrated consistently high accuracy in predicting recurrence, with an AUC of 0.85; 95% CI 0.82-0.88, 0.83; 95% CI 0.80-0.86, and 0.85; 95% CI 0.83-0.88. For patients with a high MCNN-score of recurrence, it was associated with poorer DFS with P < 0.0001 and hazard ratios of 0.1964 (95% CI: 0.1439-0.2680), 0.3249 (95% CI: 0.1896-0.5565), and 0.3458 (95% CI: 0.2582-0.4632). CONCLUSION The MCNN approach demonstrated high performance in predicting peritoneal recurrence and DFS in patients with AOC.
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Affiliation(s)
- Rui Yin
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; School of Biomedical Engineering & Technology, Tianjin Medical University, Tianjin 300203, China
| | - Zhaoxiang Dou
- Department of Breast Imaging, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Yanyan Wang
- Department of CT and MRI, Shanxi Tumor Hospital, Taiyuan 030013, China
| | - Qian Zhang
- Department of Radiology, Baoding No. 1 Central Hospital, Baoding 071030, China
| | - Yijun Guo
- Department of Breast Imaging, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Yigeng Wang
- Department of Radiology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Ying Chen
- Department of Gynecologic Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Chao Zhang
- Department of Bone Cancer, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Huiyang Li
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xiqi Jian
- School of Biomedical Engineering & Technology, Tianjin Medical University, Tianjin 300203, China
| | - Lisha Qi
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Wenjuan Ma
- Department of Breast Imaging, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
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Niu X, Ma F, Li F, Wei C, Zhang J, Gao Z, Wang J, Da M. Integration of bioinformatics and cellular experiments unveils the role of SYT12 in gastric cancer. BMC Cancer 2024; 24:1331. [PMID: 39472897 PMCID: PMC11520883 DOI: 10.1186/s12885-024-13077-w] [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: 07/09/2024] [Accepted: 10/18/2024] [Indexed: 11/02/2024] Open
Abstract
OBJECTIVE This study employs integrated bioinformatics analysis and in vitro cellular experiments to elucidate the role of Synaptotagmin-12 (SYT12) in the progression of gastric cancer. METHODS We utilized databases and platforms such as Xiantao Academic Tools, UALCAN, Kaplan-Meier plotter analysis, and The Cancer Genome Atlas (TCGA) to extract datasets on SYT12 in gastric cancer. We analyzed the relationship between SYT12 expression and the clinicopathological features, prognosis, diagnosis, and immune infiltration of stomach adenocarcinoma (STAD) patients. Verification was conducted using samples from 31 gastric cancer patients. Additionally, in vitro cellular experiments were performed to determine the role and potential mechanisms of SYT12 in the malignant behavior of gastric cancer cells. RESULTS Comprehensive bioinformatics analysis indicated that SYT12 is highly expressed in most cancers and is associated with promoter DeoxyriboNucleic Acid (DNA) methylation levels. SYT12 expression correlated with clinicopathological features, immune cell infiltration, immune checkpoint gene expression, and poor prognosis in STAD patients. In vitro experiments suggest that SYT12 may promote the proliferation and migration of gastric cancer cells by inducing epithelial-mesenchymal transition (EMT). CONCLUSIONS This study highlights the significant role of SYT12 in gastric cancer, suggesting its potential as a new target for early diagnosis, treatment, immunological, and prognostic evaluation in gastric cancer, offering new insights for precision medicine in this disease.
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Affiliation(s)
- Xingdong Niu
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, China
| | - Fubin Ma
- School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
| | - Fangying Li
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, China
| | - Cunchun Wei
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, China
| | - Junrui Zhang
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, China
| | - Zhenhua Gao
- Department of General Surgery, The First People's Hospital of Baiyin (Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine), Baiyin, China
| | - Junhong Wang
- The First Clinical Medical College, Lanzhou University, 222 Tianshui South Road, Lanzhou, 730000, China.
- Department of General Surgery, The First People's Hospital of Baiyin (Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine), Baiyin, China.
| | - Mingxu Da
- The First Clinical Medical College, Lanzhou University, 222 Tianshui South Road, Lanzhou, 730000, China.
- Department of Surgical Oncology, Gansu Provincial Hospital, Donggang West Road, 204, lanzhou, Lanzhou, China.
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Baj J, Kołodziej M, Kobak J, Januszewski J, Syty K, Portincasa P, Forma A. Significance of Immune and Non-Immune Cell Stroma as a Microenvironment of Hepatocellular Carcinoma-From Inflammation to Hepatocellular Carcinoma Progression. Int J Mol Sci 2024; 25:10233. [PMID: 39408564 PMCID: PMC11475949 DOI: 10.3390/ijms251910233] [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: 07/28/2024] [Revised: 09/19/2024] [Accepted: 09/20/2024] [Indexed: 10/20/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver cancer as well as the most prevalent cause of death in the adult patient population with cirrhosis. The occurrence of HCC is primarily caused by chronic liver inflammation that might occur because of a viral infection, non-alcoholic fatty liver disease (NAFLD), or various lifestyle-associated factors. The objective of this review was to summarize the current knowledge regarding the microenvironment of HCC, indicating how immune- and non-immune-cell stroma might affect the onset and progression of HCC. Therefore, in the following narrative review, we described the role of tumor-infiltrating neutrophils, bone-marrow-derived cells, tumor-associated mast cells, cancer-associated fibroblasts, tumor-associated macrophages, liver-sinusoidal endothelial cells, lymphocytes, and certain cytokines in liver inflammation and the further progression to HCC. A better understanding of the HCC microenvironment might be crucial to introducing novel treatment strategies or combined therapies that could lead to more effective clinical outcomes.
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Affiliation(s)
- Jacek Baj
- Department of Correct, Clinical and Imaging Anatomy, Chair of Fundamental Sciences, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (J.B.); (J.J.)
| | - Magdalena Kołodziej
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (M.K.); (J.K.)
| | - Joanna Kobak
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (M.K.); (J.K.)
| | - Jacek Januszewski
- Department of Correct, Clinical and Imaging Anatomy, Chair of Fundamental Sciences, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (J.B.); (J.J.)
| | - Kinga Syty
- Institute of Health Sciences, John Paul the II Catholic University of Lublin, Konstantynów 1G, 20-708 Lublin, Poland;
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy;
| | - Alicja Forma
- Chair and Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland; (M.K.); (J.K.)
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Kang W, Wang C, Wang M, Liu M, Hu W, Liang X, Zhang Y. The CXCR2 chemokine receptor: A new target for gastric cancer therapy. Cytokine 2024; 181:156675. [PMID: 38896956 DOI: 10.1016/j.cyto.2024.156675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/21/2024] [Accepted: 06/05/2024] [Indexed: 06/21/2024]
Abstract
Gastric cancer (GC) is one of the most common malignant tumors in the world, and current treatments are still based on surgery and drug therapy. However, due to the complexity of immunosuppression and drug resistance, the treatment of gastric cancer still faces great challenges. Chemokine receptor 2 (CXCR2) is one of the most common therapeutic targets in targeted therapy. As a G protein-coupled receptor, CXCR2 and its ligands play important roles in tumorigenesis and progression. The abnormal expression of these genes in cancer plays a decisive role in the recruitment and activation of white blood cells, angiogenesis, and cancer cell proliferation, and CXCR2 is involved in various stages of tumor development. Therefore, interfering with the interaction between CXCR2 and its ligands is considered a possible target for the treatment of various tumors, including gastric cancer.
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Affiliation(s)
- Wenyan Kang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang Hunan, China
| | - Chengkun Wang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang Hunan, China
| | - Minhui Wang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang Hunan, China
| | - Meiqi Liu
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang Hunan, China
| | - Wei Hu
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang Hunan, China
| | - Xiaoqiu Liang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang Hunan, China.
| | - Yang Zhang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang Hunan, China.
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11
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Mousset A, Albrengues J. Neutrophil extracellular traps modulate chemotherapy efficacy and its adverse side effects. Biol Cell 2024; 116:e2400031. [PMID: 38724262 DOI: 10.1111/boc.202400031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 07/13/2024]
Abstract
Neutrophils, major regulator of innate immunity have recently emerged as key components of the tumor microenvironment. The role of neutrophils in cancer has been linked to their ability to form neutrophil extracellular traps (NETs), structures composed of decondensed DNA decorated with enzymes that are released into the extracellular space. Here, we discuss the pivotal roles of NETs, in influencing responses to chemotherapy and its severe adverse effect. Highlighting recent insights, we discuss the dual nature of NETs in the context of chemotherapy treatment, examining their potential to either counteract or enhance treatment outcomes. Strategic targeting of NETs emerges as a promising avenue for determining combination therapies that could help counteracting resistance or enhancing chemotherapy efficacy as well as limiting complications due to this type of treatment.
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Affiliation(s)
- Alexandra Mousset
- Institute for Research on Cancer and Aging, University Côte d'Azur, Nice, France
| | - Jean Albrengues
- Institute for Research on Cancer and Aging, University Côte d'Azur, Nice, France
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12
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Wu Z, Zhu Z, Wu W, Hu S, Cao J, Huang X, Xie Q, Deng C. CELSR3 is a prognostic marker in HNSCC and correlates with immune cell infiltration in the tumor microenvironment. Eur Arch Otorhinolaryngol 2024; 281:3143-3156. [PMID: 38507078 PMCID: PMC11065926 DOI: 10.1007/s00405-024-08566-4] [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: 11/24/2023] [Accepted: 02/17/2024] [Indexed: 03/22/2024]
Abstract
PURPOSE To look at the diagnostic value of the CELSR receptor 3 (CELSR3) gene in head and neck squamous cell carcinoma (HNSCC) and its effect on tumor immune invasion, which is important for enhancing HNSCC treatment. METHODS Several bioinformatics tools were employed to investigate CELSR3's putative oncogenic pathway in HNSCC, and datasets from The Tumor Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), Gene Expression Profile Interaction Analysis (GEPIA) and LinkedOmics were extracted and evaluated. CELSR3 has been linked to tumor immune cell infiltration, immunological checkpoints, and immune-related genes. CELSR3's putative roles were investigated using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and pathway enrichment analysis. The expression level of CELSR3 in HNSCC tissues and cells was detected by RT-qPCR. The effects of CELSR3 on proliferation of HNSCC cells were detected by CCK-8 assay. RESULTS CELSR3 was shown to be expressed differently in different types of cancer and normal tissues. CELSR3 gene expression was linked to pN-stage and pM-stage. Patients with high CELSR3 expression also have a well prognosis. CELSR3 expression was found to be an independent predictive factor for HNSCC in both univariate and multivariate Cox regression analyses. We discovered the functional network of CELSR3 in HNSCC using GO and KEGG analysis. CELSR3 expression levels were found to be favorably associated with immune cell infiltration levels. Furthermore, CELSR3 expression levels were significantly correlated with the expression levels of many immune molecules, such as MHC genes, immune activation genes, chemokine receptors, and chemokines. CELSR3 is highly expressed in HNSCC tissues and cells. CELSR3 overexpression significantly inhibited the proliferation of HNSCC cells. CELSR3 expression may affect the immune microenvironment and, as a result, the prognosis of HNSCC. CONCLUSION CELSR3 expression is elevated in HNSCC tumor tissues, and high CELSR3 expression is associated with well prognosis, which inhibited the proliferation of NHSCC cells. CELSR3 has the potential to influence tumor formation by controlling tumor-infiltrating cells in the tumor microenvironment (TME). As a result, CELSR3 may have diagnostic significance in HNSCC.
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Affiliation(s)
- Zhongbiao Wu
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China.
| | - Zhongyan Zhu
- Department of Rehabilitation, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanchang, 330003, China
| | - Weikun Wu
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China
| | - Shiping Hu
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China
| | - Jian Cao
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China
| | - Xinmei Huang
- Department of Otolaryngology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330019, China
| | - Qiang Xie
- Department of Otolaryngology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330019, China
| | - Chengcheng Deng
- Department of Otolaryngology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330019, China
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13
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Ma W, Hu J. Downregulated CDH3 is correlated with a better prognosis for LUAD and decreases proliferation and migration of lung cancer cells. Genes Genomics 2024; 46:713-731. [PMID: 38064156 DOI: 10.1007/s13258-023-01476-5] [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: 05/04/2023] [Accepted: 11/05/2023] [Indexed: 05/19/2024]
Abstract
BACKGROUND CDH3 is a glycoprotein with a single-span transmembrane domain that mediates cell-to-cell adhesion. Abnormal expression of CDH3 is associated with a poor prognosis in patients with breast, thyroid, colorectal carcinomas and glioblastoma. Soluble CDH3 in pleural effusions can be used as a marker for real-time monitoring of resistance to first- and second-generation EGFR-TKIs. The CDH3 mechanism underlying lung adenocarcinomas (LUADs) has not been established. OBJECTIVE This study analyzed the correlation between CDH3 expression and lung cancer prognosis and the effect of down-regulation CDH3 expression on the proliferation and migration of lung cancer cells. METHODS CDH3 expression was studied using the Oncomine, TIMER, PanglaoDB, and GEPIA databases. The effect of CDH3 on clinical prognosis was assessed with GEPIA, the PrognoScan database, and Kaplan-Meier plotter. The relationship between CDH3 to immune infiltrating cells was explored using TIMER and TISIDB. The function of CDH3 in lung cancer cell lines was determined by CCK-8 and wound healing assays in vitro. Furthermore, RNA sequencing was used to identify key signaling pathways and differentially-expressed genes. RESULTS LUAD tissues had higher CDH3 expression compared with normal tissues and were associated with worse overall survival in patients with LUAD. CDH3 expression had positive associations with infiltration of CD4 + T cells, Tregs and exhausted T cells, but negative associations with infiltration of B cells in patients with LUAD. CCK-8 and wound healing assays revealed that downregulation of CDH3 inhibited the proliferation and migration of cells. KEGG analysis revealed that the TGF-beta signaling pathways were demonstrated to be enriched pathways for genes negatively regulated by knockdown of CDH3. CONCLUSION CDH3 expression affects proliferation and migration of lung cancer cells and might serve as a potential prognostic marker in LUAD patients.
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Affiliation(s)
- Wanru Ma
- Department of Blood Transfusion, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Da Hua Road, Dong Dan, Beijing, 100730, People's Republic of China
| | - Junhua Hu
- Department of Blood Transfusion, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Da Hua Road, Dong Dan, Beijing, 100730, People's Republic of China.
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14
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He K, Xie MY, Gao XJ, Wang H, Li JD. The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma. Pharmgenomics Pers Med 2024; 17:271-288. [PMID: 38827182 PMCID: PMC11141762 DOI: 10.2147/pgpm.s456965] [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: 02/01/2024] [Accepted: 05/18/2024] [Indexed: 06/04/2024] Open
Abstract
Introduction Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.
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Affiliation(s)
- Kun He
- Institute of Hepatobiliary, Pancreatic and Intestinal Diseases, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
| | - Meng-yi Xie
- Institute of Hepatobiliary, Pancreatic and Intestinal Diseases, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
| | - Xiao-jin Gao
- Institute of Hepatobiliary, Pancreatic and Intestinal Diseases, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
| | - Hao Wang
- Institute of Hepatobiliary, Pancreatic and Intestinal Diseases, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
| | - Jing-dong Li
- Institute of Hepatobiliary, Pancreatic and Intestinal Diseases, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
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15
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Gao M, Liang X, Fan M, Wu Y, Dong MY, Du RL. Exploring the potential biological function of GRK2 in colorectal cancer. Funct Integr Genomics 2024; 24:51. [PMID: 38446273 DOI: 10.1007/s10142-024-01322-1] [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: 08/08/2023] [Revised: 02/07/2024] [Accepted: 02/14/2024] [Indexed: 03/07/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) is a malignant tumor of the gastrointestinal tract with high morbidity and mortality. There is growing evidence that GRK2 plays a key role in the development and progression of several human cancers. However, the role and potential mechanisms of GRK2 in colon cancer (COAD) are unclear. METHODS The expression data of GRK2 was downloaded from The Cancer Genome Atlas database (TCGA). Variation in GRK2 was explored based on the cBioPortal database. The TIMER and TISCH2 databases were used to analyse the relationship between GRK2 expression and tumor immune microenvironment (TME). A log-rank test was used to compare the prognosis of high and low expression of GRK2 groups. Detecting the effect of GRK2 on cell cycle and apoptosis induced by 5-Fluorouracil (5-FU) through the flow cytometry and detection of apoptosis-related molecules by Western blot. RESULTS We demonstrated that GRK2 has a potential oncogenic role. GRK2 expression was upregulated in COAD, which predicted poorer overall survival in COAD patients. The cellular assays showed that GRK2 plays a role in the growth and proliferation of colon cancer cells, also the expression of GRK2 have relationship with the sensitivity of 5-FU and cell cycle progression. CONCLUSIONS Our results suggest that high GRK2 expression is closely associated with the development of tumor and affects the 5-FU sensitivity.
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Affiliation(s)
- Meng Gao
- Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China
| | - Xinyi Liang
- Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China
| | - Mengqi Fan
- Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China
| | - Yutong Wu
- Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China
| | - Ming-You Dong
- Reproductive Medicine, Guangxi Medical and health key discipline construction project of the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China.
| | - Run-Lei Du
- Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China.
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16
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Lin Z, Ji X, Tian N, Gan Y, Ke L. APOB is a potential prognostic biomarker in hepatocellular carcinoma. Discov Oncol 2024; 15:28. [PMID: 38310202 PMCID: PMC10838261 DOI: 10.1007/s12672-024-00877-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 01/30/2024] [Indexed: 02/05/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is significantly associated with adverse prognostic outcomes. The development and progression of different types of human tumors are significantly influenced by APOB. Nevertheless, the significance and pathomechanisms of APOB in HCC have not been conclusively determined. We assessed APOB expression levels in HCC using three publicly available databases of TIMER2.0, UALCAN and Human Protein Atlas. To identify the biological function of APOB, we conducted enrichment analysis via LinkedOmics. Moreover, UALCAN was employed to assess the relationship between APOB expression and clinicopathological features among HCC patients. Additionally, the Kaplan-Meier plotter was utilized to investigate the prognostic relevance of APOB in HCC. To explore potential regulatory ncRNAs that could bind to APOB, we utilized StarBase and GEPIA. Furthermore, the correlation between APOB expression and immune cell infiltration, as well as immune checkpoint genes, was investigated using Spearman's correlation analysis in TISIDB, GEPIA, and TIMER2.0. The findings of our investigation showed a notable decrease in the expression levels of APOB among individuals diagnosed with HCC. Moreover, a noteworthy correlation was observed between the expression of APOB and immune checkpoint genes, alongside the occurrence of immune cell infiltration. The levels of APOB expression in HCC tissues also showed correlations with various clinicopathological features. According to Cox regression analysis, decreased APOB expression emerged as a potential autonomous predictor for OS, RFS, DSS, and PFS among HCC patients. Furthermore, we identified six potential pathways associated with non-coding RNA (ncRNA) as the most promising pathway for APOB in HCC. Our results illuminate the possible involvement of APOB in HCC and offer understanding into its governing mechanisms and medical importance.
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Affiliation(s)
- Zhifeng Lin
- Department of Medical Record; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Xiaohui Ji
- Department of Obstetrics and Gynaecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Nana Tian
- Department of Medical Record, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yu Gan
- Department of Medical Record, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Li Ke
- Department of Medical Record; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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17
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Liu J, Wang M, Wang M, Wang F, Zhang B. LncRNAs-Regulated High Expression of LAMC2 Reveals a Prognostic and Immunological Value in Pancreatic Adenocarcinoma. Biochem Genet 2024; 62:485-503. [PMID: 37382751 DOI: 10.1007/s10528-023-10435-4] [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: 04/21/2023] [Accepted: 06/18/2023] [Indexed: 06/30/2023]
Abstract
Pancreatic adenocarcinoma (PAAD) is one of the most hazardous cancers in digestive system, and the prognosis is notoriously bad. Increasing evidences indicate that Laminin Subunit Gamma 2 (LAMC2) is critical for the initiation and the growth of various sorts of human cancers. However, the involved molecular pathways of LAMC2 in PAAD are still poorly understood. In this study, prediction programs and databases were employed to conduct pan-cancer analysis. Multiple variations of human malignancies showed increased LAMC2 expression, which was positively correlated to a poor prognosis in PAAD. Moreover, LAMC2 was positively correlated with the biomarkers of immune cells including CD19, CD163, and NOS2 in PAAD. The lncRNA C5orf66 /PTPRG-AS1- miR-128-3p -LAMC2 axis was identified to be a potential upstream regulatory pathway of LAMC2 in PAAD. Furthermore, LAMC2 upregulation in PAAD was associated with PD-L1 expression, indicating promoting carcinoma immune cell infiltration. Our study elucidated prognostic and immunological values of LAMC2 in PAAD, providing a promise target for PAAD treatment.
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Affiliation(s)
- Jingyun Liu
- School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Mengyue Wang
- School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Miaowen Wang
- School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Fu Wang
- School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
- Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis, School of Pharmacy, Shaanxi Institute of International Trade and Commerce, Xianyang, 712046, China.
| | - Beilei Zhang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
- Department of Obstetrics and Gynecology, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, Shaanxi, China.
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Zhao R, Hu Z, Zhang X, Huang S, Yu G, Wu Z, Yu W, Lu J, Ruan B. The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors. Cell Commun Signal 2024; 22:68. [PMID: 38273295 PMCID: PMC10809652 DOI: 10.1186/s12964-023-01421-9] [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: 09/06/2023] [Accepted: 12/03/2023] [Indexed: 01/27/2024] Open
Abstract
Digestive tract tumors are heterogeneous and involve the dysregulation of multiple signaling pathways. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a notable role in the oncogenesis of digestive tract tumors. Typically activated by pro-inflammatory cytokines, it regulates important biological processes, such as cell growth, differentiation, apoptosis, immune responses, and inflammation. The aberrant activation of this pathway manifests in different forms, including mutations in JAKs, overexpression of cytokine receptors, and sustained STAT activation, and contributes to promoting the malignant characteristics of cancer cells, including uncontrolled proliferation, resistance to apoptosis, enhanced invasion and metastasis, angiogenesis, acquisition of stem-like properties, and drug resistance. Numerous studies have shown that aberrant activation of the JAK-STAT pathway is closely related to the development and progression of digestive tract tumors, contributing to tumor survival, angiogenesis, changes in the tumor microenvironment, and even immune escape processes. In addition, this signaling pathway also affects the sensitivity of digestive tract tumors to chemotherapy and targeted therapy. Therefore, it is crucial to comprehensively understand the oncogenic mechanisms underlying the JAK-STAT pathway in order to develop effective therapeutic strategies against digestive tract tumors. Currently, several JAK-STAT inhibitors are undergoing clinical and preclinical trials as potential treatments for various human diseases. However, further investigation is required to determine the role of this pathway, as well as the effectiveness and safety of its inhibitors, especially in the context of digestive tract tumors. In this review, we provide an overview of the structure, classic activation, and negative regulation of the JAK-STAT pathway. Furthermore, we discuss the pathogenic mechanisms of JAK-STAT signaling in different digestive tract tumors, with the aim of identifying potential novel therapeutic targets. Video Abstract.
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Affiliation(s)
- Ruihong Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China
| | - Zhangmin Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China
| | - Xiaoli Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China
| | - Shujuan Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China
| | - Guodong Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China
| | - Zhe Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China
| | - Wei Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China
| | - Juan Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China.
| | - Bing Ruan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310003, China.
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Wang B, Zhu Y, Wang S, Li Z, Wang L, Rao W, Cheng N, Chen R, Ying J, Xue L. Gastric tubular adenocarcinoma with diffuse neutrophils infiltrating: characteristics and probable treatment strategy. Gastric Cancer 2024; 27:86-101. [PMID: 38019350 DOI: 10.1007/s10120-023-01446-6] [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: 03/06/2023] [Accepted: 10/09/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Gastric adenocarcinoma is a highly heterogeneous malignancy with varying prognoses. In clinicopathological practice, we noticed a special tubular adenocarcinoma with diffuse neutrophils infiltrating (TADNI). However, the proportion and characteristics of TADNI remain unclear. This study aimed to evaluate the features of TADNI and explore probable treatments. METHODS We divided 289 tubular adenocarcinoma cases into the TADNI and non-TADNI (nTADNI) groups by histological neutrophil quantity and performed immunohistochemistry of treatment-associated markers (CXCR1, CXCR2, PD-L1, CD8, HER2 and VEGFR2). Then we evaluated the clinical and morphological features in these cases. We also compared the value of histological features and peripheral blood neutrophil test. In addition, multiomics bioinformatic analyses were performed using the public datasets. RESULTS In our cohort, TADNI accounted for 10.4% of all tubular adenocarcinoma cases. These cases had worse prognoses (especially the neutrophils mainly outside the tubes) than nTADNI cases. The histological identification of TADNI had more prognostic value than peripheral blood neutrophils. CXCR1/CXCR2 expression was significantly high in TADNI group which indicated that CXCR1/CXCR2 inhibitors might be beneficial for TADNI patients. There were no significant differences in the expression of PD-L1, CD8, HER2 and VEGFR2. The analyses of TCGA data confirmed that TADNI cases had poorer prognoses and higher CXCR1/CXCR2 expression. Bioinformatic results also revealed molecular features (more hsa-mir-223 expression, fewer CD8-positive T cells and regulatory T cells, tighter communication between tumor cells' CXCR1/CXCR2 and neutrophils' CXCL5/CXCL8) of this type. CONCLUSIONS TADNI is a special morphological subtype with poorer prognoses and unique molecular characteristics, which might benefit from CXCR1/CXCR2 inhibitors.
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Affiliation(s)
- Bingzhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yongjian Zhu
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Shaoming Wang
- Office of 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, 100021, China
| | - Zhuo Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Long Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Wei Rao
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Na Cheng
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Rongshan Chen
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Wu Z, You C, Zhu Z, Wu W, Cao J, Xie Q, Deng C, Huang X, Hu S. SLA2 is a prognostic marker in HNSCC and correlates with immune cell infiltration in the tumor microenvironment. Eur Arch Otorhinolaryngol 2024; 281:427-440. [PMID: 37688682 PMCID: PMC10764518 DOI: 10.1007/s00405-023-08213-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 08/25/2023] [Indexed: 09/11/2023]
Abstract
PURPOSE To investigate Src-like adaptor 2 gene (SLA2) expression in head and neck squamous cell carcinoma (HNSCC), its potential prognostic value, and its effect on immune cell infiltration. METHODS Through a variety of bioinformatics analyses, we extracted and analyzed data sets from the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), and Gene Expression Profile Interaction Analysis (GEPIA) to analyze the correlation between SLA2 and the prognosis, immune checkpoint, tumor microenvironment (TME) and immune cell infiltration of HNSCC, and to explore its potential oncogenic mechanism. To further explore the potential role of SLA2 in HNSCC by Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS SLA2 messenger ribonucleic acid (mRNA) levels were increased in HNSCC tumor tissues compared with normal tissues. In addition, we found that SLA2 may be an independent prognostic factor for HNSCC, and high SLA2 expression is associated with favorable prognosis in HNSCC. SLA2 expression was positively correlated with B cells, cluster of differentiation 8-positive T cells (CD8 + T cells), cluster of differentiation 4-positive T cells (CD4 + T cells), macrophages, neutrophil and dendritic cells infiltration. SLA2 has also been shown to co-express immune-related genes and immune checkpoints. Significant GO term analysis by Gene Set Enrichment Analysis (GSEA) indicated that genes correlated with SLA2 were located mainly in the side of membrane, receptor complex, secretory granule membrane, endocytic vesicle, membrane region, and endosome membrane, where they were involved in leukocyte cell-cell adhesion, response to interferon-gamma, and regulation of immune effector process. These related genes also served as antigen binding, cytokine receptor activity, phosphatidylinositol 3-kinase activity, peptide receptor activity, Src homology domain 3 (SH3) domain binding, and cytokine receptor binding. KEGG pathway analysis demonstrated that these genes related to SLA2 were mainly enriched in signal pathways, such as hematopoietic cell lineage, cell adhesion molecules (CAMs), natural killer cell mediated cytotoxicity, measles, and chemokine signaling pathway. CONCLUSIONS SLA2 is increased in HNSCC, and high SLA2 expression is associated with favorable prognosis. SLA2 may affect tumor development by regulating tumor infiltrating cells in TME. SLA2 may be a potential target for immunotherapy.
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Affiliation(s)
- Zhongbiao Wu
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China
| | - Chengkun You
- Department of Neurology, Pinghu Hospital of Traditional Chinese Medicine, Jiaxing, 314200, China
| | - Zhongyan Zhu
- Department of Rehabilitation, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanchang, 330003, China
| | - Weikun Wu
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China
| | - Jian Cao
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China
| | - Qiang Xie
- Department of Otolaryngology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330019, China
| | - Chengcheng Deng
- Department of Otolaryngology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330019, China
| | - Xinmei Huang
- Department of Otolaryngology, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi, China
| | - Shiping Hu
- Department of Otolaryngology, Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, 90 Bayi Avenue, Xihu District, Nanchang, 330003, Jiangxi, China.
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Liu X, Wang ZZ, Meng S, Zang F, Zhang H, Wang J, Chen YZ. Systematic analysis reveals distinct roles of USF family proteins in various cancer types. Int J Biol Markers 2023; 38:243-252. [PMID: 37846061 DOI: 10.1177/03936155231206135] [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: 10/18/2023]
Abstract
BACKGROUND Upstream stimulatory factors (USFs) are members of the basic helix-loop-helix leucine zipper transcription factor family, including USF1, USF2, and USF3. The first two members have been well studied compared to the third member, USF3, which has received scarce attention in cancer research to date. Despite a recently reported association of its alteration with thyroid carcinoma, its expression has not been previously analyzed. METHODS We comprehensively analyzed differential levels of USFs expression, genomic alteration, DNA methylation, and their prognostic value across different cancer types and the possible correlation with tumor-infiltrating immune cells and drug response by using different bioinformatics tools. RESULTS Our findings established that USFs play an important role in cancers related to the urinary system and justify the necessity for further investigation. We implemented and offer a useful ShinyApp to facilitate researchers' efforts to inquire about any other gene of interest and to perform the analysis of drug response in a user-friendly fashion at http://zzdlab.com:3838/Drugdiscovery/.
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Affiliation(s)
- Xia Liu
- Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's clinical research center for cancer, Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Zhuo-Zhi Wang
- School of Biomedical Engineering, Tianjin Medical University, Tianjin, China
| | - Shuai Meng
- Department of Pharmacy, Key Laboratory of Cancer Prevention and Therapy, Tianjin's clinical research center for cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Fenglin Zang
- Department of Pathology, Key Laboratory of Cancer Prevention and Therapy, Tianjin's clinical research center for cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Huilai Zhang
- Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's clinical research center for cancer, Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China
| | - Ju Wang
- School of Biomedical Engineering, Tianjin Medical University, Tianjin, China
| | - Yong-Zi Chen
- Laboratory of Tumor Cell Biology, Key Laboratory of Cancer Prevention and Therapy, Tianjin's clinical research center for cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
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22
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Zhao B, Wang S, Xue L, Wang Q, Liu Y, Xu Q, Xue Q. EFHD1 expression is correlated with tumor-infiltrating neutrophils and predicts prognosis in gastric cancer. Heliyon 2023; 9:e21062. [PMID: 37876466 PMCID: PMC10590971 DOI: 10.1016/j.heliyon.2023.e21062] [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: 07/16/2023] [Revised: 10/09/2023] [Accepted: 10/13/2023] [Indexed: 10/26/2023] Open
Abstract
Background Gastric cancer (GC) ranks third in terms of mortality worldwide. The tumor microenvironment is critical for the progression of gastric cancer. This study investigated the association between EF-hand domain containing 1 (EFHD1) expression and its clinical significance in the tumor microenvironment (TME) of gastric cancer. Methods We used bioinformatic analyses to assess the relevance of EFHD1 mRNA in the TME of gastric carcinoma tissues and its relationship with clinical features. Therefore, we performed multiplex immunohistochemistry analyses to determine the potential role of the EFHD1 protein in the TME of gastric cancer. Results EFHD1 expression increased dramatically in gastric cancer tissues compared to levels in non-cancerous tissue samples (t = 6.246, P < 0.001). The EFHD1 protein presentation was associated with invasion depth (χ2 = 19.120, P < 0.001) and TNM stages (χ2 = 14.468, P = 0.002). Notably, EFHD1 protein expression was significantly related to CD66b + neutrophil infiltration of the intratumoral (r = 0.420, P < 0.001) and stromal (r = 0.367, P < 0.001) TME in gastric cancer. Additionally, Cox regression analysis revealed that EFHD1 was an independent prognostic predictor (hazard ratio [HR] = 2.262, P < 0.001) in patients with gastric cancer. Conclusions Our study revealed the pattern of EFHD1 overexpression in the TME of patients with gastric cancer and demonstrated its utility as a biomarker for unfavorable clinical outcomes, thereby providing a potential immunotherapy target.
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Affiliation(s)
- Bin Zhao
- Department of Pathology, Nantong Tumor Hospital, Nantong Fifth People's Hospital, Affiliated Tumor Hospital of Nantong University, Jiangsu, 226361, China
| | - Shanshan Wang
- Department of General Surgery, The Affiliated Suqian Hospital of Xuzhou Medical University and Nanjing Drum Tower Hospital Group Suqian Hospital, Suqian, 223800, China
| | - Li Xue
- Department of Pathology, Nantong Tumor Hospital, Nantong Fifth People's Hospital, Affiliated Tumor Hospital of Nantong University, Jiangsu, 226361, China
| | - Qingqing Wang
- Department of General Surgery, Affiliated Hospital of Nantong University & Medical School of Nantong University, Jiangsu, 226001, China
| | - Yushan Liu
- Department of Pathology, Nantong Tumor Hospital, Nantong Fifth People's Hospital, Affiliated Tumor Hospital of Nantong University, Jiangsu, 226361, China
| | - Qiang Xu
- Department of Pathology, Nantong Tumor Hospital, Nantong Fifth People's Hospital, Affiliated Tumor Hospital of Nantong University, Jiangsu, 226361, China
| | - Qiu Xue
- Department of General Surgery, Nantong Tumor Hospital, Nantong Fifth People's Hospital, Affiliated Tumor Hospital of Nantong University, Jiangsu, 226361, China
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23
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Chen L, Wu Z, Guo J, Wang X, Zhao Z, Liang H, Zhang R, Deng J. Initial clinical and experimental analyses of ALDOA in gastric cancer, as a novel prognostic biomarker and potential therapeutic target. Clin Exp Med 2023; 23:2443-2456. [PMID: 36422738 DOI: 10.1007/s10238-022-00952-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 11/15/2022] [Indexed: 11/25/2022]
Abstract
The effect of ALDOA, an important regulator of tumor metabolism and immune cell function, on gastric cancer (GC) immune infiltration has not been elucidated. Hence, we explored the feasibility of using ALDOA combined with immune molecular markers as novel prognostic or therapeutic targets for GC patients. Bioinformatic analyses were initially performed in multiple databases to assess the prognostic prediction values of ALDOA expression in GC. Subsequently, both ALDOA expression and the clinicopathological characteristics of a total of 114 GC patients who underwent curative gastrectomy were collected to demonstrate the potential association between ALDOA expression and the biological behaviors of GC. Next, the expression of ALDOA and its effect on prognosis were determined at the mRNA and protein levels, respectively, using tissue microarrays and cellular experiments. Subsequently, several molecular mechanisms were revealed based on elaborate analyses, indicating that ALDOA expression was potentially involved in the progression of GC and could be considered a promising biomarker for evaluating the prognosis of GC. High ALDOA expression was frequently found in GC cells and GC tissues at the mRNA and protein levels. Based on survival analysis, the expression of ALDOA indicated comparatively poor overall survival (OS) in GC and was identified as an independent prognostic predictor of GC. Correlation analysis showed that ALDOA expression had a positive association with lymph node metastasis in GC patients. Additionally, microRNA-1179 was found to play a key role in inhibiting the expression of ALDOA in the metabolic pathways of GC cells, which might disrupt the expression of various immune molecules and be detrimental to the prognosis of GC. ALDOA should be considered a promising molecular target for evaluating the prognosis of GC, owing to its potential role in immune regulation.
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Affiliation(s)
- Liqiao Chen
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Zizhen Wu
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Jiamei Guo
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Xinyu Wang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Zhenzhen Zhao
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Han Liang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Rupeng Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Jingyu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China.
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.
- Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.
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Liu S, Wu W, Du Y, Yin H, Chen Q, Yu W, Wang W, Yu J, Liu L, Lou W, Pu N. The evolution and heterogeneity of neutrophils in cancers: origins, subsets, functions, orchestrations and clinical applications. Mol Cancer 2023; 22:148. [PMID: 37679744 PMCID: PMC10483725 DOI: 10.1186/s12943-023-01843-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 08/14/2023] [Indexed: 09/09/2023] Open
Abstract
Neutrophils, the most prevalent innate immune cells in humans, have garnered significant attention in recent years due to their involvement in cancer progression. This comprehensive review aimed to elucidate the important roles and underlying mechanisms of neutrophils in cancer from the perspective of their whole life cycle, tracking them from development in the bone marrow to circulation and finally to the tumor microenvironment (TME). Based on an understanding of their heterogeneity, we described the relationship between abnormal neutrophils and clinical manifestations in cancer. Specifically, we explored the function, origin, and polarization of neutrophils within the TME. Furthermore, we also undertook an extensive analysis of the intricate relationship between neutrophils and clinical management, including neutrophil-based clinical treatment strategies. In conclusion, we firmly assert that directing future research endeavors towards comprehending the remarkable heterogeneity exhibited by neutrophils is of paramount importance.
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Affiliation(s)
- Siyao Liu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Wenchuan Wu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yueshan Du
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Hanlin Yin
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Qiangda Chen
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Weisheng Yu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Wenquan Wang
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Jun Yu
- Departments of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Liang Liu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China.
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China.
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Ning Pu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China.
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
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Fang ZX, Hou YY, Wu Z, Wu BX, Deng Y, Wu HT, Liu J. Immune responses of six-transmembrane epithelial antigen of the prostate 4 functions as a novel biomarker in gastric cancer. World J Clin Oncol 2023; 14:297-310. [PMID: 37700807 PMCID: PMC10494559 DOI: 10.5306/wjco.v14.i8.297] [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: 05/10/2023] [Revised: 06/19/2023] [Accepted: 07/19/2023] [Indexed: 08/22/2023] Open
Abstract
BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells. According to emerging evidence, six-transmembrane epithelial antigen of the prostate 4 (STEAP4) performs a crucial part in tumor microenvironmental immune response and tumorigenesis, and serves as the potential target for cellular and antibody immunotherapy. However, the immunotherapeutic role of STEAP4 in gastric cancer (GC) remains unclear. AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells, and explore the potential value of STEAP4 as an immune prognostic indicator in GC. METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients. Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature. R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC (GSE62254) by the ESTIMATE algorithm, and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis. RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues, and STEAP4 expression was positively correlated with the clinical stage of GC. In GC, the expression of STEAP4 was positively correlated with the infiltration levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. The expression level of STEAP4 was strongly correlated with most of the immune markers. In addition, STEAP4 expression was inversely correlated with tumor purity, but correlated with stromal score (r = 0.43, P < 0.001), immune score (r = 0.29, P < 0.001) and estimate score (r = 0.39, P < 0.001). Moreover, stromal, immune, and estimate scores were higher in the STEAP4 high expression group, whereas tumor purity was higher in the STEAP4 Low expression group. The relationship between STEAP4 expression and prognosis of patients with GC was further investigated, and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival. In addition, Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC. CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC, with significantly high levels being associated with poor prognosis. Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells, which may contribute to the regulation of the tumor microenvironment. In conclusion, STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration, as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.
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Affiliation(s)
- Ze-Xuan Fang
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yan-Yu Hou
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Zheng Wu
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Bing-Xuan Wu
- Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu Deng
- Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Hua-Tao Wu
- Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jing Liu
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
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Fu F, Zhang Y, Feng J, Nie Y. Bioinformatics analysis of hedgehog interacting protein in colorectal cancer: a study based on GEO data and TCGA data. BMC Gastroenterol 2023; 23:278. [PMID: 37568084 PMCID: PMC10422795 DOI: 10.1186/s12876-023-02867-4] [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: 03/17/2023] [Accepted: 06/30/2023] [Indexed: 08/13/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Hedgehog Interacting Protein (HHIP) is evolutionarily conserved protein, which are important morphogens for a wide range of developmental processes,However, the specific role and mechanism of HHIP in CRC remains not fully understood. In this study, we first performed pan-cancer analysis for HHIP's expression via The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) data and found that HHIP might be a potential anti-oncogene for CRC. Subsequently, non-coding RNAs (ncRNAs) contributing to down-regulated HHIP expression were identified through a combination of a series of in silico analyses, including expression and correlation analysis. Finally, the LINC02381/miR-577 complex was identified as the top potential upstream regulator of HHIP in CRC. In addition, HHIP expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. Overall, our findings clarified ncRNAs-mediated down-regulation of HHIP which was associated with poor prognosis and tumor immune infiltration in CRC.
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Affiliation(s)
- Fengyihuan Fu
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, China
| | - Yuan Zhang
- Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, Institute of Gastroenterology, Zhejiang University, Hangzhou, 310000, China
| | - Jubin Feng
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, China.
| | - Yuqiang Nie
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, No. 1 Panfu Road, Yuexiu District, Guangzhou, 510180, Guangdong, China.
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Qiu J, Wang Z, Zhao L, Zhang P, Xu Y, Xia Q. High C1QTNF1 expression mediated by potential ncRNAs is associated with poor prognosis and tumor immunity in kidney renal clear cell carcinoma. Front Mol Biosci 2023; 10:1201155. [PMID: 37529377 PMCID: PMC10387556 DOI: 10.3389/fmolb.2023.1201155] [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: 04/06/2023] [Accepted: 07/07/2023] [Indexed: 08/03/2023] Open
Abstract
Background: Kidney renal clear cell carcinoma (KIRC) originates from proximal tubular cells and is the most common subtype of renal cell carcinoma. KIRC is characterized by changes in lipid metabolism, and obesity is a risk factor for it. C1q And TNF Related 1 (C1QTNF1), a novel adipokine and member of the C1q and TNF-related protein (CTRP) family, has been shown to affect the progression of various cancers. However, the role of C1QTNF1 in KIRC has not been studied. Methods: The Wilcoxon rank sum test was used to analyze the expression of C1QTNF1 in KIRC tissues and normal tissues. The relationship between clinicopathological features and C1QTNF1 levels was also examined by logistic regression and the Wilcoxon rank sum test. In addition, the effect of C1QTNF1 on the prognosis of KIRC patients was analyzed by Kaplan-Meier (KM). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the potential signaling pathways and biological functions of differential genes. A nomogram was constructed to predict the prognosis of KIRC patients. Spearman correlation analysis was performed to determine the association between C1QTNF1 expression and immune cell infiltration and immune checkpoint genes. The upstream miRNAs and lncRNAs of C1QTNF1 were predicted by the ENCORI online tool. Finally, we examined the proliferation, invasion, and migration abilities of KIRC cells after C1QTNF1 knockdown. Results: The expression of C1QTNF1 in KIRC tissues was significantly higher than in normal renal tissues. Patients with higher C1QTNF1 expression had a poor prognosis, a finding supported by Kaplan-Meier survival analysis. C1QTNF1 expression was significantly correlated with TNM and pathologic stages, age, and gender (p < 0.05). The C1QTNF1 expression level was significantly correlated with immune cell infiltration and immune checkpoint genes in KIRC. Additionally, high C1QTNF1 expression was associated with poor prognosis in stage I and II, T1 and T2, T3 and T4, N0, and M0 patients (HR > 1, p < 0.05). The calibration diagram shows that the C1QTNF1 model has effective predictive performance for the survival of KIRC patients. Knockdown of C1QTNF1 inhibited KIRC cell proliferation, cell migration, and cell invasion. In addition, CYTOR and AC040970.1/hsa-miR-27b-3p axis were identified as the most likely upstream ncRNA-related pathways of C1QTNF1 in KIRC. Conclusion: In conclusion, our study suggests that high expression of C1QTNF1 is associated with KIRC progression and immune infiltration. The increased expression of C1QTNF1 suggests a poor prognosis in KIRC patients.
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Affiliation(s)
- Jiechuan Qiu
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Zicheng Wang
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Leizuo Zhao
- Department of Urology, Dongying People’s Hospital, Dongying, China
- Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Peizhi Zhang
- Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yingkun Xu
- Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qinghua Xia
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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Bai M, Liu X. Diagnostic biomarker KIF23 is associated with immune infiltration and immunotherapy response in gastric cancer. Front Oncol 2023; 13:1191009. [PMID: 37483517 PMCID: PMC10361780 DOI: 10.3389/fonc.2023.1191009] [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: 03/21/2023] [Accepted: 06/12/2023] [Indexed: 07/25/2023] Open
Abstract
Kinesin family member 23 (KIF23), an index of tumor proliferation, can serve as a prognostic marker in numerous tumors. However, the relationship between KIF23 expression and diagnostic value, immune infiltration, and immunotherapy response remains unclear in gastric cancer(GC). We primarily demonstrated that GC tissue had higher levels of KIF23 expression than the adjacent normal tissue on mRNA and protein levels. The ROC analysis revealed KIF23 had an outstanding diagnostic value of GC in the training and validation set (AUC = 0.958, and AUC = 0.86793, respectively). We discovered that KIF23 was positively associated with age, histological type, and H. pylori infection of GC. Subsequently, the KIF23 expression level was correlated with the gene mutation, function enrichment, immune cell infiltration, and immune cell marker of GC based on multiple online websites and R software. KIF23 expression was related to the infiltration of CD8+ T cells, CD4+T cells, macrophages, and dendritic cells in GC. Especially, KIF23 expression was positively significantly associated with the Th1 cell marker STAT1 (Signal transducer and activator of transcription 1). Patients with high KIF23 expression exhibited greater immune cell infiltrates, including T cell CD4+ memory helper, Treg, and M1 cells, which indicated that high KIF23 expression is more conducive to immunosuppression. Finally, KIF23 expression had a positive relationship with TMB and MSI, and affected the immune microenvironment in GC tissues by increased expression of ICPs such as CD274(PD-L1), CTLA4, HAVCR2, and LAG3. Our study uncovered that KIF23 can serve as an immune-related biomarker for diagnosis and immunotherapy response of GC.
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Affiliation(s)
- Maoshu Bai
- Department of Oncology, Dazhou Integrated Traditional Chinese Medicine and Western Medicine Hospital, Dazhou Second People’s Hospital, Dazhou, Sichuan, China
| | - Xin Liu
- Molecular Diagnosis Center, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, Yunnan, China
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Zhu L, Wang Z, Han W, Xu A. Comprehensive analysis of the biological function and immune infiltration of SLC38A2 in gastric cancer. BMC Gastroenterol 2023; 23:74. [PMID: 36918802 PMCID: PMC10015769 DOI: 10.1186/s12876-023-02689-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 02/22/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Solute carrier family 38 member 2 (SLC38A2) has previously been reported to participate in carcinogenesis. However, its expression and function in gastric cancer (GC) remain unclear. The present study aimed to investigate the role of SLC38A2 in GC. METHODS The prognostic value and expression of SLC38A2 in GC was analyzed by combining bioinformatics and experimental analyses. Colony formation, Cell Counting Kit-8, wound healing, Transwell and tumor formation assays were performed to assess the biological function of SLC38A2. The cBioPortal, GeneMANIA and LinkedOmics databases were mined to determine the underlying regulatory mechanisms of SLC38A2. The role of SLC38A2 in tumor immune infiltration was explored using the TIMER database. RESULTS Our results demonstrated that SLC38A2 was upregulated and was correlated with a poor prognosis in GC patients. SLC38A2 downregulation significantly inhibited the proliferation, invasion and migration of GC cells. Abnormal genetic alteration and epigenetic regulation may contribute to the upregulation of SLC38A2 expression levels in GC. The results of enrichment analysis demonstrated that SLC38A2 was associated with 'hippo signaling' and 'ubiquitinyl hydrolase activity'. The results also indicated that SLC38A2 may be a key factor in GC immune infiltration and M2 macrophage polarization. CONCLUSION Overall, these data identified that SLC38A2 may serve as a potential prognostic biomarker and therapeutic target in GC.
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Affiliation(s)
- Liang Zhu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230001, People's Republic of China
| | - Zhengguang Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230001, People's Republic of China
| | - Wenxiu Han
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230001, People's Republic of China
| | - Aman Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230001, People's Republic of China.
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30
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Zhao YX, Xu BW, Wang FQ, Jiang FY, Xu JW, Yu DX. nc-RNA-mediated high expression of CDK6 correlates with poor prognosis and immune infiltration in pancreatic cancer. Cancer Med 2023; 12:5110-5123. [PMID: 36457244 PMCID: PMC9972169 DOI: 10.1002/cam4.5260] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 08/25/2022] [Accepted: 09/08/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Emerging evidence manifests that cyclin-dependent kinase 6 (CDK6) plays an essential part in the initiation and progression of several types of human cancer, and its descending expression is correlated with an adverse prognosis. However, the precise role of CDK6 in Pancreatic cancer (PC) remains obscure. AIMS To identify the potential ceRNA regulatory axis of CDK6 in PC and explore its relationship with immune cells and immune checkpoints. MATERIALS & METHODS Using The Cancer Genome Atlas TCGA and GTEx data analyze the expression and survival of CDK6 in patients in pan-cancer, and cellular experiments were performed to verify the effect of CDK6 on cell function. Using GEPIA and STARBASE databases to analyze prognosis, expression and survival, and identify non coding RNA (ncRNA) that mediates CDK6 overexpression. The TIMER 2.0 database was used for immune correlation analysis. RESULTS We revealed CDK6 might be an oncogene in PC, and the HOXA11-AS /NR2F1-AS1- miR-454-3p axis was identified as the possible upstream ncRNA-associated pathway of CDK6 in PC. In addition, CDK6 show significant association with three immune checkpoints (PD-L1, PD-L2, and HAVCR2), the infiltration level of immune cells, and immunity biomarkers. DISCUSSION We discussed some applications of CDK6 in breast cancer, melanoma, and hemorrhagic malignancies. The role of miR-15a-5p, HOXA11-AS and NR2F1-AS1 in tumor development was also discussed based on existing studies. The potential mechanism of CDK6 affecting immune cells in pancreatic cancer was discussed. CONCLUSIONS Overall, these results established that nc-RNA-mediated high expression of CDK6 is associated with patient outcomes and immune invasion in pancreatic cancer.
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Affiliation(s)
- Yu-Xuan Zhao
- Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Bo-Wen Xu
- Department of Hepatobiliary Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Fang-Qing Wang
- Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Feng-Yang Jiang
- Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jian-Wei Xu
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - De-Xin Yu
- Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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31
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Wang X, Li X, Wu Y, Hong J, Zhang M. The prognostic significance of tumor-associated neutrophils and circulating neutrophils in glioblastoma (WHO CNS5 classification). BMC Cancer 2023; 23:20. [PMID: 36609243 PMCID: PMC9817270 DOI: 10.1186/s12885-022-10492-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 12/27/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Tumor-associated neutrophils (TANs) in the tumor microenvironment are prognostic biomarkers in many malignancies. However, it is unclear whether TANs can serve as a prognostic marker for clinical outcomes in patients with glioblastoma (GBM), as classified according to World Health Organization Classification of Tumors of the Central Nervous System, fifth edition (CNS5). In the present study, we analyzed correlations of TANs and peripheral blood neutrophils prior to radiotherapy with overall survival (OS) in GBM (CNS5). METHODS RNA-seq expression profiles of patients with newly diagnosed GBM (CNS5) were extracted from The Cancer Genome Atlas (TCGA), and The Chinese Glioma Genome Atlas (CGGA). TAN infiltration was inferred using CIBERSORTx algorithm. Neutrophil counts prior to radiotherapy in newly diagnosed GBM (CNS5) were obtained from the First Affiliated Hospital of Fujian Medical University. The prognostic value of TANs and peripheral blood neutrophils before radiotherapy was investigated using Kaplan-Meier analysis and Cox proportional hazards models. The robustness of these findings was evaluated by sensitivity analysis, and E values were calculated. RESULTS A total of 146 and 173 individuals with GBM (CNS5) were identified from the TCGA and CGGA cohorts, respectively. High infiltration of TANs was of prognostic of poor OS in TCGA (HR = 1.621, 95% CI: 1.004-2.619) and CGGA (HR = 1.546, 95% CI: 1.029-2.323). Levels of peripheral blood neutrophils before radiotherapy (HR = 2.073, 95% CI: 1.077-3.990) were independently associated with poor prognosis. Sensitivity analysis determined that the E-value of high TANs infiltration was 2.140 and 2.465 in the TCGA and CGGA cohorts. CONCLUSIONS TANs and peripheral blood neutrophil levels before radiotherapy are prognostic of poor outcomes in GBM (CNS5).
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Affiliation(s)
- Xuezhen Wang
- grid.412683.a0000 0004 1758 0400Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China ,grid.412683.a0000 0004 1758 0400Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xiaoxia Li
- grid.412683.a0000 0004 1758 0400Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China ,grid.412683.a0000 0004 1758 0400Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yufan Wu
- grid.412683.a0000 0004 1758 0400Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China ,grid.412683.a0000 0004 1758 0400Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jinsheng Hong
- grid.412683.a0000 0004 1758 0400Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China ,grid.412683.a0000 0004 1758 0400Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China ,grid.412683.a0000 0004 1758 0400Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Mingwei Zhang
- grid.412683.a0000 0004 1758 0400Department of Radiotherapy, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China ,grid.412683.a0000 0004 1758 0400Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China ,grid.412683.a0000 0004 1758 0400Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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Zhang Y, Wang H, Lu J, Lv Q, Yun B, Ge Z, Yan L. Down-regulation of S1PR2 is correlated with poor prognosis and immune infiltrates in cervical squamous cell carcinoma and endocervical adenocarcinoma. Int J Immunopathol Pharmacol 2023; 37:3946320231178131. [PMID: 37232164 PMCID: PMC10226337 DOI: 10.1177/03946320231178131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 05/09/2023] [Indexed: 05/27/2023] Open
Abstract
Objectives: Cervical squamous cell carcinoma and cervical adenocarcinoma (CESC) are the second leading cause of deaths from malignant tumors in women, while their therapeutic and diagnostic aims are still finited. A growing body of evidence indicated that sphingosine-1-phosphate receptor 2 (S1PR2) plays essential roles in the occurrence and development about several human cancers. Nevertheless, the key mechanism and role mechanism of S1PR2 in CESC are still unclear.Methods: We first used Tissue Expression (GTEx) and Genotypic Cancer Genome Atlas (TCGA) data to perform pan-cancer analysis on the expression and prognosis of S1PR2, and found that S1PR2 may have a potential impact on CESC. To generate a protein-protein interaction (PPI) network using the STRING database. The clusterProfiler package is used for feature-rich analysis. The Tumor IMmune Estimation Resource was used to determine the connection between S1PR2 mRNA expression and immune infiltrates. Results: S1PR2 expression in CESC tissues was down-regulated compared with adjacent normal tissues. Kaplan-Meier analysis indicated that compared with patients with high expression of S1PR2, CESC patients with low S1PR2 expression had a worse prognosis. Reduced S1PR2 expression is associated with patients with high clinical stage, more histological types of squamous cell carcinoma, and poor primary treatment outcomes. The receiver operating characteristic curve of S1PR2 was 0.870. Correlation analysis showed that the mRNA expression of S1PR2 was related to immune infiltrates and tumor purity.Conclusion: Down-regulated S1PR2 expression is related to poor survival and immune infiltration in CESC. S1PR2 is a potential biomarker for poor prognosis and as a potential target for CESC immune therapy.
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Affiliation(s)
- Yu Zhang
- Department of Emergency Medicine, Pudong New District Gongli Hospital of
Shanghai, Shanghai, China
| | - Haichuan Wang
- Department of General Surgery, Pudong New District Gongli Hospital of
Shanghai, Shanghai, China
| | - Jie Lu
- Department of General Surgery, Pudong New District Gongli Hospital of
Shanghai, Shanghai, China
| | - Qiang Lv
- Department of General Surgery, Pudong New District Gongli Hospital of
Shanghai, Shanghai, China
| | - Bei Yun
- Department of General Surgery, Pudong New District Gongli Hospital of
Shanghai, Shanghai, China
| | - Zhiru Ge
- Department of Cardiology, Pudong New District Gongli Hospital of
Shanghai, Shanghai, China
| | - Li Yan
- Department of Cardiology, Pudong New District Gongli Hospital of
Shanghai, Shanghai, China
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33
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Zhang Y, Zhang L, Zhao Y, Wang S, Feng L. Overexpression of LILRA2 indicated poor prognosis of ovarian carcinoma: A new potential biomarker and therapeutic target. Taiwan J Obstet Gynecol 2023; 62:77-88. [PMID: 36720556 DOI: 10.1016/j.tjog.2022.10.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2022] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVE This study aimed to assess the role of leukocyte immunoglobulin-like receptor A2 (LILRA2) in ovarian carcinoma (OC) oncogenesis and prognosis. MATERIALS AND METHODS Using the Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, the association between clinicopathological profiles and LILRA2 expression was investigated using logistic regression analysis. Kaplan-Meier analysis, Cox regression analysis, and column plots predicted the clinical outcomes of patients with OC and determine the predictive value of LILRA2. The biological functions of LILRA2 were assessed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. We used single-sample Gene Set Enrichment Analysis to investigate the relationship between immune cell infiltration and LILRA2 expression. RESULTS LILRA2 expression in OC tumors was significantly higher than in normal tissue (P < 0.05). The high LILRA2 expression in OC was correlated with lymphatic invasion (P = 0.014). The results showed consistency indices of 0.611 [95% confidence interval (CI), 0.572-0.649] and 0.623 (95% CI, 0.584-0.663) for the overall and disease-specific survival nomograms, respectively. Cox regression analysis showed that LILRA2 was an independent risk factor for overall survival (hazard ratio [HR], 1.511; P = 0.002) and disease-specific survival (HR, 1.537; P = 0.003). Functional annotation revealed enrichment with immunoglobulin-corresponding pathways when LILRA2 expression was high. CONCLUSION By evaluating gene expression profiles, we demonstrated that LILRA2 has considerable potential to act as a therapeutic target and prognostic biomarker in OC.
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Affiliation(s)
- Yixin Zhang
- Department of Medical Ultrasound, Shandong First Medical University, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Medicine and Health Key Laboratory of Abdominal Medical Imaging, No.16766, Jingshi Road, Jinan, Shandong Province, China
| | - Li Zhang
- Department of Medical Ultrasound, Shandong First Medical University, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Medicine and Health Key Laboratory of Abdominal Medical Imaging, No.16766, Jingshi Road, Jinan, Shandong Province, China
| | - Yuli Zhao
- Department of Medical Ultrasound, Shandong First Medical University, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Medicine and Health Key Laboratory of Abdominal Medical Imaging, No.16766, Jingshi Road, Jinan, Shandong Province, China
| | - Sen Wang
- Department of Medical Ultrasound, Shandong First Medical University, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Medicine and Health Key Laboratory of Abdominal Medical Imaging, No.16766, Jingshi Road, Jinan, Shandong Province, China
| | - Li Feng
- Department of Medical Ultrasound, Shandong First Medical University, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qian Foshan Hospital, Shandong Medicine and Health Key Laboratory of Abdominal Medical Imaging, No.16766, Jingshi Road, Jinan, Shandong Province, China.
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MACC1 Correlates with Tumor Progression and Immune Cell Infiltration of Colon Adenocarcinoma and is Regulated by the lncRNA ZFAS1/miR-642a-5p Axis. JOURNAL OF ONCOLOGY 2022; 2022:8179208. [PMID: 36545127 PMCID: PMC9763013 DOI: 10.1155/2022/8179208] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 10/27/2022] [Accepted: 11/08/2022] [Indexed: 12/14/2022]
Abstract
Colon adenocarcinoma (COAD) is the most common pathologic type of colon cancer. Metastasis is responsible for the high mortality rate of patients with COAD. The gene, metastasis-associated in colon cancer 1 (MACC1), is a biomarker predictive of both metastatic and metastasis-free survival in patients with colon cancer and other solid tumors. However, the underlying mechanism by which MACC1 affect COAD progression and metastasis remains unknown. In this study, we analyzed the expression level and prognostic value of MACC1, as well as their correlation, in patients with various types of cancer included in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. High MACC1 expression was found to be significantly associated with poor prognosis in patients with COAD. Analysis of the potential upstream miRNA of MACC1 showed that miR-642a-5p was downregulated in COAD and was negatively correlated with MACC1 expression. Analysis of the upstream regulators of miR-642a-5p showed that the long non-coding RNA (lncRNA) ZFAS1was the most likely upstream regulator of miR-642a-5p. In addition, the expression of MACC1 correlated positively with tumor immune cell infiltration, as well as with the levels of biomarkers of five kinds of immune cells. In summary, these findings suggest that MACC1 contributes to COAD progression and immune cell infiltration via the ZFAS1/miR-642a-5p/MACC1 axis.
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Chen Q, Yin H, Liu S, Shoucair S, Ding N, Ji Y, Zhang J, Wang D, Kuang T, Xu X, Yu J, Wu W, Pu N, Lou W. Prognostic value of tumor-associated N1/N2 neutrophil plasticity in patients following radical resection of pancreas ductal adenocarcinoma. J Immunother Cancer 2022; 10:jitc-2022-005798. [PMID: 36600557 PMCID: PMC9730407 DOI: 10.1136/jitc-2022-005798] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/03/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND As an integral part of the tumor microenvironment (TME), tumor-associated neutrophils play a crucial role in tumor development. The objective of this study was to investigate the plasticity of tumor-associated N1 and N2 neutrophils in the TME of pancreatic ductal adenocarcinoma (PDAC), along with its impact on survival and association with immune infiltrations. METHODS The primary and validation cohorts including 90 radical resection patients from September 2012 to May 2016 and 29 radical resection patients from September 2018 to October 2019, respectively, with complete survival data, were enrolled. Immunofluorescence staining was used to identify tumor-associated N1 and N2 neutrophils, and the N1/N2 ratio was used to evaluate N1 and N2 plasticity. Thereafter, the association between tumor-associated N1/N2 neutrophil plasticity, clinical features, and immune infiltrations was investigated. RESULTS There was a significant increase in tumor-associated N2 neutrophils compared with tumor-associated N1 neutrophils. Low N1/N2 ratios were associated with the poorer differentiation of tumors, easier lymph node metastases, and a higher TNM stage. The median overall survival (OS) and recurrence-free survival (RFS) of the high tumor-associated N1 neutrophil group were significantly longer than those of the low group, while the tumor-associated N2 neutrophils played an opposite role. The multivariable analysis revealed that a high N1/N2 ratio was a significant prognostic indicator for OS and RFS. In addition, tumor-associated N1/N2 neutrophils showed an opposite correlation with tumor-infiltrating CD8+ T cells and Tregs. CONCLUSION The plasticity of tumor-associated N1/N2 neutrophils was identified as a crucial prognostic indicator that might reflect the TME and immune escape in patients with PDAC. On further investigation and validation, our findings may be used to further stratify patients with varying prognoses to optimize treatment.
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Affiliation(s)
- Qiangda Chen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hanlin Yin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Siyao Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sami Shoucair
- Department of Surgery, MedStar Health, Baltimore, Maryland, USA,Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ni Ding
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China,Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jicheng Zhang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tiantao Kuang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xuefeng Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jun Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,Departments of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Wenchuan Wu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ning Pu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
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Fan Z, Yu B, Pan T, Li F, Li J, Hou J, Liu W, Su L, Zhu Z, Yan C, Liu B. DKK1 as a robust predictor for adjuvant platinum chemotherapy benefit in resectable pStage II-III gastric cancer. Transl Oncol 2022; 27:101577. [PMID: 36332599 PMCID: PMC9636483 DOI: 10.1016/j.tranon.2022.101577] [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: 08/24/2022] [Revised: 10/05/2022] [Accepted: 10/19/2022] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND Adjuvant chemotherapy (ACT) with 5-FU alone or 5-FU plus platinum after curative surgery improves the prognosis of pStage II-III gastric cancer (GC). However, only a subset of patients benefits from adjuvant platinum. To avoid the side effects of platinum, it is significant to accurately screen the patients who would benefit maximally with this treatment. The present study aimed to assess the value of DKK1 in predicting the benefit of adjuvant platinum chemotherapy in patients with pStage II -III GC. METHODS Platinum sensitivity-related genes were screened by bioinformatics. DKK1 expression in 380 GC specimens was detected by immunohistochemistry (IHC) staining, and the correlation with adjuvant platinum-specific benefits were analyzed. RESULTS DKK1 was screened as the most significant platinum sensitivity-related gene. In patients with DKK1high GC, the estimated absolute 5-year overall survival (OS) benefits from adjuvant platinum for pStage II-III, II, IIIA, IIIB, and IIIC were 25.5%, 17.3%, 36.4%, 29.2% and 31.1%, respectively, and the estimated absolute 5-year disease-free survival (DFS) benefits in the corresponding stages were 27.4%, 17.5%, 36.7%, 29.7% and 31.5%, respectively. These benefits were significantly higher than those in the same TNM stage without adjusting for DKK1 status. The performance of DKK1 was independent of the TNM stage and other clinicopathological variables. Similar results were obtained in the TCGA and ACRG cohorts. Furthermore, nomograms were constructed to predict the survival benefits in DKK1 subgroups. CONCLUSIONS The stratification strategy based on DKK1 status is more precise than the TNM staging system for the selection of pStage II-III GC patients suitable for platinum-containing ACT.
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Affiliation(s)
- Zhiyuan Fan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China,Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Beiqin Yu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Tao Pan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Fangyuan Li
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jianfang Li
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Junyi Hou
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wentao Liu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Liping Su
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhenggang Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Chao Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China,Corresponding authors.
| | - Bingya Liu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China,Corresponding authors.
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Yuan Z, Wang L, Chen C. Analysis of the prognostic, diagnostic and immunological role of HSP90α in malignant tumors. Front Oncol 2022; 12:963719. [PMID: 36158677 PMCID: PMC9499179 DOI: 10.3389/fonc.2022.963719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
Heat shock protein 90α (HSP90α) encoded by the HSP90AA1 gene, is the stress inducible isoform of the molecular chaperone HSP90, and was demonstrated as a promising hallmark to diagnose, prognosis in malignant tumors. This study is to evaluate the value of HSP90α in diagnosis, prognosis and immunotherapy of malignant tumors by investigating the expression of HSP90α in plasma of various tumors and analyzing the expression of HSP90α at gene and protein levels via pan-cancer database. We founded that levels of HSP90α in malignant tumors groups were significantly higher than healthy controls in serum. Pan-cancer analysis showed that HSP90AA1 was highly expressed in 27 of 33 tumors, but low in individual cancers (such as renal malignancies). The plasma HSP90α level was positively correlated with the stage of malignant tumor, but there was no significant difference between HSP90AA1 and the stage of most tumors. Cox regression analysis showed that HSP90AA1 expression was significantly correlated with OS in only 6 of the 32 cancers, including LIHC, KIRC, HNSC, LUAD, BRCA and MESO. Up-regulation of HSP90AA1 in most tumors was positively correlated with PDCD1LG2 and CD274 immune checkpoint genes. T cell CD8+ was positively correlated with HSP90AA1 in COAD, DLBC and UVM, and negatively correlated with HSP90AA1 in ESCA, GBM, HNSC, KIRC, KIRP, UCEC and STAD. The AUC of HSP90α are generally high in different tumor groups, which indicated its diagnostic value in malignant tumors. In conclusion, serum HSP90α in patients with malignant tumor is generally elevated, which is of positive significance as an independent diagnosis and combined diagnosis. However, we found that the expression level of HSP90AA1 gene in most tumors was not completely consistent with the serum level, and even down-regulated in some tumors. Plasma levels can be used as biomarkers of poor prognosis in some tumors, but it cannot be used as a biomarker for poor prognosis of all tumors, and more in-depth studies are needed.
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Affiliation(s)
- Zhimin Yuan
- Xi’an Jiaotong University, Xi’an, China
- Department of Clinical Laboratory, Shaanxi Provincial Cancer Hospital, Xi’an, China
| | - Longhao Wang
- Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Cheng Chen
- Department of General Dentistry/Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, China
- *Correspondence: Cheng Chen,
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38
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Gao Z, Wang L, Song Z, Ren M, Yang Y, Li J, Shen K, Li Y, Ding Y, Yang Y, Zhou Y, Wei C, Gu J. Intratumoral CD73: An immune checkpoint shaping an inhibitory tumor microenvironment and implicating poor prognosis in Chinese melanoma cohorts. Front Immunol 2022; 13:954039. [PMID: 36131912 PMCID: PMC9483101 DOI: 10.3389/fimmu.2022.954039] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 07/18/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundAs a novel immune checkpoint, CD73 has been reported to play prominent roles in several malignancies. However, the significance of CD73 in melanoma remains ambiguous. This study sought to reveal the impact of CD73 on the tumor microenvironment (TME) and patients’ prognosis, and to investigate whether CD73 could be a therapeutic target in Chinese melanomas, which were dominated by acral and mucosal subtypes.MethodsTwo independent Chinese cohorts of 194 patients with melanoma were enrolled. CD73 and PD-L1 expression as well as CD8+ and CD56+ cell infiltrations were evaluated by immunohistochemistry in 194 resected melanoma samples. Clinical outcomes of patients were assessed utilizing the Kaplan-Meier plotter and Cox proportional hazard analysis. RNA-seq data was obtained from TCGA database. Gene set functional annotations were performed based on GO, KEGG and GSEA analysis. CIBERSORT, ssGSEA and TIMER were used to explore the association between CD73 and immune infiltration. These findings were validated by establishing tumor xenograft model, and functions of tumor-infiltrating immune cells were examined by flow cytometry and immunofluorescence.ResultsHigh CD73 expression showed poorer clinical outcomes and was identified as an independent prognostic indicator for survival in two cohorts. Expression of CD73 was more prevalent than PD-L1 in Chinese melanoma cohorts (54.6% vs 23.2%). Co-expression of both immune checkpoints was infrequent (12.9%) in melanoma, and 54.4% of PD-L1 negative cases showed elevated expression of CD73. CD73high tumors showed a microenvironment with fewer CD8+ T cells and CD56+ NK cells infiltration, which displayed a dysfunctional phenotype. With the treatment of CD73 inhibitor APCP, the amount of CD8+ T cells and CD56+ NK cells infiltrated in tumors was elevated and the immunosuppressive effect of CD73 was eliminated.ConclusionsHigh CD73 expression was associated with an inhibitory TME and adverse clinical outcomes of melanoma. In comparison to PD-L1, CD73 was more prevalent and possessed more definite prognostic significance. Therefore, it may serve as a prognostic indicator and immunotherapeutic target next to PD-L1 in melanoma for Chinese population.
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Affiliation(s)
- Zixu Gao
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lu Wang
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhengqing Song
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ming Ren
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yang Yang
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianrui Li
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kangjie Shen
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yinlam Li
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yiteng Ding
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yanwen Yang
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuhong Zhou
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chuanyuan Wei
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- *Correspondence: Jianying Gu, ; Chuanyuan Wei,
| | - Jianying Gu
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- *Correspondence: Jianying Gu, ; Chuanyuan Wei,
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Jian F, Yanhong J, Limeng W, Guoping N, Yiqing T, Hao L, Zhaoji P. TIMP2 is associated with prognosis and immune infiltrates of gastric and colon cancer. Int Immunopharmacol 2022; 110:109008. [PMID: 35792273 DOI: 10.1016/j.intimp.2022.109008] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/24/2022] [Accepted: 06/25/2022] [Indexed: 02/07/2023]
Abstract
Tissue inhibitor of metalloproteinase-2 (TIMP2), a member of tissue inhibitors of the metalloproteinase (TIMP) family is associated with the progression of various tumors. However, the association of TIMP2 with cancer prognosis and tumor-infiltrating lymphocytes remains unclear. TIMP2 expression was analyzed by Tumor Immune Estimation Resource (TIMER), TNM plot, Gene Expression Profiling Interactive Analysis (GEPIA) database, and 50 paired gastric cancer tissues. We evaluated the influence of TIMP2 on clinical prognosis using the Kaplan-Meier plotter, the PrognoScan database, GEPIA, and TCGA data. The correlation of TIMP2 with tumor immune infiltrates and the set of gene markers of immune infiltrates was investigated by TIMER and GEPIA. TIMP2 is highly expressed in gastric cancer and slightly expressed in colon cancer. High TIMP2 expression was significantly correlated with poor overall survival (OS, hazard ratio [HR] = 1.38, 95% confidence interval [CI]: [1.16-1.63]; P = 0.0002) and progression-free survival (PFS, HR = 1.39, 95% CI: [1.14-1.7]; P = 0.0012) in gastric cancers. Specifically, high TIMP2 expression was associated with poorer OS and PFS, but not with OS and PFS in stage 1 (OS HR = 1.96, P = 0.29; PFS HR = 0.43, P = 0.19) and stage 2 (OS HR = 1.59, P = 0.12; PFS HR = 1.47, P = 0.2) and stage N0 patients (OS HR = 1.6, P = 0.35; PFS HR = 1.56, P = 0.38) of gastric cancer patients. There was a significant positive correlation between TIMP2 expression and different types of immune cells, including CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in the stomach adenocarcinoma (STAD) and colon adenocarcinoma (COAD). Moreover, TIMP2 expression was strongly correlated with different sets of immune markers. These results suggest that TIMP2 is associated with prognosis and level of immune infiltration in a variety of cancers, especially colon and gastric cancer patients. Moreover, the expression of TIMP2 potentially contributes to the regulation of tumor-associated macrophages (TAMs), dendritic cells, T cell exhaustion, and Tregs in colon and gastric cancer. These findings suggest that TIMP2 may serve as a prognostic biomarker for predicting prognosis and immune infiltration in gastric and colon cancer.
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Affiliation(s)
- Fang Jian
- Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 230022, Anhui, China
| | - Jiao Yanhong
- School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China
| | - Wei Limeng
- Second Clinical Medical College, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China
| | - Niu Guoping
- Clinical Laboratory, Xuzhou Central Hospital; Xhzhou clinical school of Xuzhou medical university, 199 Jiefang South Road, Xuzhou 221000, Jiangsu, China
| | - Tian Yiqing
- Clinical Laboratory, Xuzhou Central Hospital; Xhzhou clinical school of Xuzhou medical university, 199 Jiefang South Road, Xuzhou 221000, Jiangsu, China.
| | - Lin Hao
- Department of Gastrointestinalsurgery, Xuzhou Central Hospital; Xhzhou clinical school of Xuzhou medical university, 199 Jiefang South Road, Xuzhou 221000, Jiangsu, China.
| | - Pan Zhaoji
- Clinical Laboratory, Xuzhou Central Hospital; Xhzhou clinical school of Xuzhou medical university, 199 Jiefang South Road, Xuzhou 221000, Jiangsu, China.
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Peng K, Ren X, Ren Q. NcRNA-mediated upregulation of CAMK2N1 is associated with poor prognosis and tumor immune infiltration of gastric cancer. Front Genet 2022; 13:888672. [PMID: 36092901 PMCID: PMC9452964 DOI: 10.3389/fgene.2022.888672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 07/26/2022] [Indexed: 11/15/2022] Open
Abstract
Gastric cancer (GC) is still notorious for its poor prognosis and aggressive characteristics. Though great developments have been made in diagnosis and therapy for GC, the prognosis of patient is still perishing. In this study, differentially expressed genes (DEGs) in GC were first screened using three Gene Expression Omnibus (GEO) datasets (GSE13911, GSE29998, and GSE26899). Second, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to validate expression of these DEGs and perform survival analysis. We selected seven candidate genes (CAMK2N1, OLFML2B, AKR7A3, CYP4X1, FMO5, MT1H, and MT1X) to carry out the next analysis. To construct the ceRNA network, we screened the most potential upstream ncRNAs of the candidate genes. A series of bioinformatics analyses, including expression analysis, correlation analysis, and survival analysis, revealed that the SNHG10–hsa-miR-378a-3p might be the most potential regulatory axis in GC. Then, the expression of CAMK2N1, miR-378a-3p, and SNHG10 was verified in GC cell lines (GES-1, MGC-803, BGC-823, HGC-27, MKN-45, and AGS) by qRT-PCR and Western blotting. We found that SNHG10 and CAMK2N1 were highly expressed in gastric cancer lines, and the miR-378a-3p was lowly expressed in BGC-823, HGC-27, and MKN-45. Furthermore, CAMK2N1 levels were significantly negatively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. In summary, our results suggest that the ncRNA-mediated high expression of CAMK2N1 is associated with poor prognosis and tumor immune infiltration of GC.
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Affiliation(s)
- Kaipeng Peng
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xiangqing Ren
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Qian Ren
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
- *Correspondence: Qian Ren,
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Cheng L, Wang Z, Nie L, Yang C, Huang H, Lin J, Zhuo D. Comprehensive analysis of MFN2 as a prognostic biomarker associated with immune cell infiltration in renal clear cell carcinoma. Int Immunopharmacol 2022; 111:109169. [PMID: 36007389 DOI: 10.1016/j.intimp.2022.109169] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Treatment of advanced kidney renal clear cell carcinoma (KIRC) remains challenging in clinic. The functional role and prognostic significance of MFN2 in KIRC are still unclear. METHODS In this study, we first performed a bioinformatic analysis to determine the expression level and prognostic value of MFN2 in KIRC using The Cancer Genome Atlas (TCGA) dataset, and then validated the MFN2 mRNA expression in our cohort of clinical tissue samples and cell lines of KIRC via RT-qPCR. Cox regression model was used to identify the independent prognostic factors. A nomogram was constructed to predict the prognosis of KIRC patients. Gene set enrichment analysis (GSEA) was performed to predict the involved functional pathways of MFN2 co-expressed genes. The association between MFN2 expression level and immune cell infiltration was assessed using the TIMER and the TIDISB databases. In addition, cell proliferation and migration abilities of two KIRC cell lines with MFN2 overexpression were evaluated by MTS and wound healing assays, respectively. RESULTS Downregulation of MFN2 was observed in KIRC tissues and cell lines compared to the normal controls. Kaplan-Meier curve analysis indicated an inferior survival outcomes in KIRC patients with lower MFN2 expression, uncovering the tumor-suppressive role of MFN2 in KIRC. Cox regression results showed that higher MFN2 expression was one of the independent protective factors in KIRC. Besides, function predictive analysis revealed that MFN2 co-expressed genes were enriched in the biological processes of energy metabolism and autophagy. Moreover, MFN2 expression was observed to be significantly associated with immune cell infiltration and a variety of markers of tumor infiltrating immune cells (TIICs) including multiple immune checkpoints in KIRC tissues. Finally, MFN2 overexpression significantly inhibited cell proliferation and migration abilities of two KIRC cell lines examined. CONCLUSION Generally, our data suggested that MFN2 may serve as a potential prognostic biomarker and therapeutic target in KIRC.
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Affiliation(s)
- Li Cheng
- Department of Urology, the First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Zicheng Wang
- Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Liang Nie
- Department of Urology, the First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Chenglin Yang
- Department of Urology, the First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Houbao Huang
- Department of Urology, the First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Jian Lin
- Department of Urology, Peking University First Hospital, Beijing, China.
| | - Dong Zhuo
- Department of Urology, the First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China.
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Analysis and Validation of TMED3 correlates with poor prognosis and tumor immune infiltration of glioma. J Cancer Res Clin Oncol 2022:10.1007/s00432-022-04257-x. [PMID: 35951089 DOI: 10.1007/s00432-022-04257-x] [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: 05/07/2022] [Accepted: 08/02/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND Glioma is the most common primary intracranial tumor. It is notorious for its high degree of malignancy, strong invasion, and poor prognosis. The transmembrane emp24 trafficking protein 3 (TMED3) belongs to the TMED family, which is responsible for intracellular protein transport and innate immune signal transmission. More and more evidence shows that TMED3 plays a key role in the tumor progression of human cancer. However, the role and potential molecular mechanism of TMED3 in glioma have not been clarified. METHODS TMED3 expression levels, clinical data, survival prognosis, prediction of upstream miRNA, and immune-related analyses were all analyzed utilizing relevant databases. Finally, a molecular cell experiment confirmed TMED3 expression in glioma. RESULTS We discovered that TMED3 is overexpressed in most tumors, including gliomas, and is associated with tumor staging and prognosis. Subsequently, a combination of a series of bioinformatics analyses, including correlation and survival analyses, identified miR-1296-5p as the most potent upstream miRNA of TMED3 in gliomas.Additionally, we analyzed the relationship between TMED3 level and tumor immune cell infiltration and immune checkpoint expression. CONCLUSION TMED3 is highly expressed in gliomas and is associated with tumor staging and affects the prognosis of patients. Therefore, the TMED3 gene may be a potential immunotherapy target and prognostic marker for gliomas.
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Lu J, Wu D, Chen S, Huang JB, Xu BB, Xue Z, Zheng HL, Lin GS, Shen LL, Lin J, Zheng CH, Li P, Wang JB, Lin JX, Chen QY, Cao LL, Xie JW, Peng JS, Huang CM. A novel hematological classifier predicting chemotherapy benefit and recurrence hazard for locally advanced gastric cancer A multicenter IPTW analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1768-1777. [PMID: 35292203 DOI: 10.1016/j.ejso.2022.01.018] [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: 09/12/2021] [Revised: 01/08/2022] [Accepted: 01/18/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Effective classifiers for the prediction of individual adjuvant chemotherapy (AC) benefits are scarce. PURPOSE This study aimed to construct a useful classifier to predict the AC benefit and recurrence hazard based on preoperative hematological indices through a multicenter database. METHODS AND RESULTS Multivariate analysis revealing GCRF (comprehensive deep learning classifier) as an independent prognostic factor associated with overall survival (OS) and disease-free survival (DFS). Locally advanced gastric cancer (LAGC) patients are categorized into the high-risk group (HRG) and low-risk group (LRG). In HRG, OS and DFS of the AC group are significantly higher than those of the non-AC group (all p˂0.05), whereas in LRG, OS and DFS of the AC group are comparable to those of the non-AC group (all p > 0.05). Furthermore, combined GCRF with 8th AJCC TNM staging system, only 650 (51.1%) patients can benefit most from AC among 1273 patients with pStage II-III. From the perspective of recurrence pattern, the recurrence rate of HRG is significantly higher than that of LRG in any recurrence type, including local recurrence, peritoneal recurrence, and distant recurrence (all p˂0.05). Furthermore, the mean time to peritoneal recurrence and lung metastasis in HRG is earlier than that in the LRG (p = 0.028 and 0.011, respectively). CONCLUSION In summary, our novel classifier based on deep learning preoperative hematological indices can predict not only the AC benefit of LAGC patients, but also the recurrence hazard after surgery. This classifier is expected to be an effective supplement to the 8th AJCC TNM staging system for the prediction of AC benefits and is helpful for clinical decision in AC individual administration. Further large-scale western studies are warranted.
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Affiliation(s)
- Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Dong Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Shi Chen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China; Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510655, China
| | - Jiao-Bao Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Bin-Bin Xu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Zhen Xue
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Guo-Sheng Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Li-Li Shen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
| | - Jun-Sheng Peng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China; Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510655, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
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Kang Y, Gan Y, Jiang Y, You J, Huang C, Chen Q, Xu X, Chen F, Chen L. Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma. BMC Cancer 2022; 22:834. [PMID: 35907786 PMCID: PMC9339200 DOI: 10.1186/s12885-022-09930-5] [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: 04/12/2022] [Accepted: 07/25/2022] [Indexed: 11/25/2022] Open
Abstract
Background Cancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated. Methods In this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells. Results The results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis. Conclusions In conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.
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Affiliation(s)
- Yanli Kang
- Department of Clinical Laboratory, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China
| | - Yuhan Gan
- Department of Clinical Laboratory, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China
| | - Yingfeng Jiang
- Department of Clinical Laboratory, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China
| | - Jianbin You
- Department of Clinical Laboratory, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China
| | - Chen Huang
- Department of Thoracic Surgery, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China
| | - Qianshun Chen
- Department of Thoracic Surgery, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China
| | - Xunyu Xu
- Department of Clinical Laboratory, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China
| | - Falin Chen
- Department of Thoracic Surgery, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China.
| | - Liangyuan Chen
- Department of Clinical Laboratory, Fujian Provincial hospital, Shengli Clinical Medical College of Fujian Medical University, No.134, East street, Gulou District, Fuzhou, 350001, China.
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Lu Y, Yu J, Dong Q, Du Y, Liang Z. DOCK4 as a Potential Biomarker Associated with Immune Infiltration in Stomach Adenocarcinoma: A Database Analysis. Int J Gen Med 2022; 15:6127-6143. [PMID: 35846794 PMCID: PMC9286484 DOI: 10.2147/ijgm.s357096] [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: 02/14/2022] [Accepted: 06/29/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose The involvement of dedicator for cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor for Rac1, in immune infiltration in stomach adenocarcinoma (STAD) remains unclear. Methods The UALCAN database was used to analyze the expression of the DOCK family. The Kaplan–Meier method and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to assess the prognostic value of the DOCK family in STAD. Furthermore, the correlation between expression of DOCK4 as well as other immune-related marker genes and tumor immune infiltration in STAD was explored using the TIMER and GEPIA websites. Subsequently, the relationship between DOCK4 expression and clinical characteristics was verified using the UALCAN database. Finally, DOCK4 mutation was analyzed via the TIMER2.0 and cBioPortal databases and the DOCK4 protein-protein interaction networks were constructed using the GeneMANIA and STRING websites. Results DOCK4 was found to be a new prognostic biomarker in STAD. DOCK4 expression in tumors was thoroughly evaluated relative to paracancerous tissues; overexpression of DOCK4 had a negative impact on the prognosis of patients with STAD. DOCK4 was found to be significantly associated with tumor immune infiltration in STAD. Conclusion In summary, DOCK4 is a potential regulator of the recruitment and regulation of immune-infiltrating cells, thus serving as a valuable prognostic biomarker in STAD.
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Affiliation(s)
- Yi Lu
- Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Jiaxi Yu
- Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Qiuping Dong
- Department of Cancer Cell Biology, Tianjin's Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Yan Du
- Department of Operating Theatre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Zheng Liang
- Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
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Zhao G. Albumin/fibrinogen ratio, a predictor of chemotherapy resistance and prognostic factor for advanced gastric cancer patients following radical gastrectomy. BMC Surg 2022; 22:207. [PMID: 35643493 PMCID: PMC9148460 DOI: 10.1186/s12893-022-01657-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/17/2022] [Indexed: 11/12/2022] Open
Abstract
Background The objective of this study was to investigate potential predictors of chemotherapy resistance in patients with advanced gastric cancer (GC) following radical gastrectomy. Methods Eligible stage II/III GC patients with adjuvant chemotherapy after radical gastrectomy were enrolled in this study. A receiver operating characteristic (ROC) curve analysis was performed to assess the predictive and optimal cut-off values of continuous variables for chemotherapy resistance. Potential risk factors for chemotherapy resistance were determined with binary univariate and multivariate analyses. Potential prognostic factors for overall survival (OS) were determined by COX regression analysis. The association between survival and AFR level was examined using the Kaplan–Meier curve analysis. Results A total of 160 patients were included in the data analysis, and 41 patients achieved chemotherapeutic resistance with an incidence of 25.6%. Pretreatment albumin/fibrinogen ratio (AFR) (cut-off value: 10.85, AUC: 0.713, P < 0.001) was a predictor for chemotherapeutic resistance by ROC curve analysis. Low AFR (< 10.85) was an independent risk factor of chemotherapeutic resistance as determined by the univariate and multivariate logistic regression analyses (OR: 2.55, 95%CI: 1.21–4.95, P = 0.005). Multivariate COX regression analyses indicated low AFR as a prognostic factor for 5-year OS (HR: 0.36, 95%CI: 0.15–0.73, P = 0.011). Low AFR was associated with poorer 5-year disease-free survival and overall survival. Conclusions This study indicated that a low level of pretreatment AFR could serve as an independent predictor of chemotherapy resistance and postoperative prognosis in GC patients following radical gastrectomy.
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You W, Ke J, Chen Y, Cai Z, Huang ZP, Hu P, Wu X. SQLE, A Key Enzyme in Cholesterol Metabolism, Correlates With Tumor Immune Infiltration and Immunotherapy Outcome of Pancreatic Adenocarcinoma. Front Immunol 2022; 13:864244. [PMID: 35720314 PMCID: PMC9204319 DOI: 10.3389/fimmu.2022.864244] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 04/26/2022] [Indexed: 12/26/2022] Open
Abstract
Background Pancreatic adenocarcinoma (PAAD) is a treatment-refractory cancer with poor prognosis. Accumulating evidence suggests that squalene epoxidase (SQLE) plays a pivotal role in the development and progression of several cancer types in humans. However, the function and underlying mechanism of SQLE in PAAD remain unclear. Methods SQLE expression data were downloaded from The Cancer Genome Atlas and the Genotype-Tissue Expression database. SQLE alterations were demonstrated based on the cBioPortal database. The upstream miRNAs regulating SQLE expression were predicted using starBase. The function of miRNA was validated by Western blotting and cell proliferation assay. The relationship between SQLE expression and biomarkers of the tumor immune microenvironment (TME) was analyzed using the TIMER and TISIDB databases. The correlation between SQLE and immunotherapy outcomes was assessed using Tumor Immune Dysfunction and Exclusion. The log-rank test was performed to compare prognosis between the high and low SQLE groups. Results We demonstrated a potential oncogenic role of SQLE. SQLE expression was upregulated in PAAD, and it predicted poor disease-free survival (DFS) and overall survival (OS) in patients with PAAD. "Amplification" was the dominant type of SQLE alteration. In addition, this alteration was closely associated with the OS, disease-specific survival, DFS, and progression-free survival of patients with PAAD. Subsequently, hsa-miR-363-3p was recognized as a critical microRNA regulating SQLE expression and thereby influencing PAAD patient outcome. In vitro experiments suggested that miR-363-3p could knock down the expression of SQLE and inhibit the proliferation of PANC-1. SQLE was significantly associated with tumor immune cell infiltration, immune checkpoints (including PD-1 and CTLA-4), and biomarkers of the TME. KEGG and GO analyses indicated that cholesterol metabolism-associated RNA functions are implicated in the mechanisms of SQLE. SQLE was inversely associated with cytotoxic lymphocytes and predicted immunotherapy outcomes. Conclusions Collectively, our results indicate that cholesterol metabolism-related overexpression of SQLE is strongly correlated with tumor immune infiltration and immunotherapy outcomes in patients with PAAD.
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Affiliation(s)
| | | | | | | | | | | | - Xiaojian Wu
- Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Wu S, Liu S, Li Y, Liu C, Pan H. Lestaurtinib Has the Potential to Inhibit the Proliferation of Hepatocellular Carcinoma Uncovered by Bioinformatics Analysis and Pharmacological Experiments. Front Cell Dev Biol 2022; 10:837428. [PMID: 35646925 PMCID: PMC9136166 DOI: 10.3389/fcell.2022.837428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/31/2022] [Indexed: 11/13/2022] Open
Abstract
Patients diagnosed with hepatocellular carcinoma (HCC) seek a satisfactory prognosis. However, most HCC patients present a risk of recurrence, thus highlighting the lack of effectiveness of current treatments and the urgent need for improved treatment options. The purpose of this study was to identify new candidate factors in the STAT family, which is involved in hepatocellular carcinogenesis, and new targets for the treatment of HCC. Bioinformatics web resources, including Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Human Protein Atlas (HPA), Tumor Immune Estimation Resource (TIMER), and GSCALite, were used to identify candidate genes among the STAT family in HCC. STAT1 was significantly overexpressed in hepatocellular carcinoma. More meaningfully, the high STAT1 expression was significantly associated with poor prognosis. Therefore, STAT1 is expected to be a therapeutic target. The JAK2 inhibitor lestaurtinib was screened by the Genomics of Cancer Drug Sensitivity Project (GDSC) analysis. Pharmacological experiments showed that lestaurtinib has the ability to prevent cell migration and colony formation from single cells. We also found that STAT1 is involved in inflammatory responses and immune cell infiltration. Immune infiltration analysis revealed a strong association between STAT1 levels and immune cell abundance, immune biomarker levels, and immune checkpoints. This study suggests that STAT1 may be a key oncogene in hepatocellular carcinoma and provides evidence that the JAK2 inhibitor lestaurtinib is a potent antiproliferative agent that warrants further investigation as a targeted therapy for HCC.
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Affiliation(s)
- Shuang Wu
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Medicine, Qingdao University, Qingdao, China
| | - Shihai Liu
- Medical Animal Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yan Li
- Department of Operation Room, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Changchang Liu
- Medical Animal Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Huazheng Pan
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China
- *Correspondence: Huazheng Pan,
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Hu X, Chen M, Ruan Q, Shi C, Pan J, Luo L. Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer. J Immunol Res 2022; 2022:2039447. [PMID: 35647201 PMCID: PMC9135576 DOI: 10.1155/2022/2039447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/24/2022] [Accepted: 04/06/2022] [Indexed: 11/17/2022] Open
Abstract
Protein PDZ and LIM domain 3 (PDLIM3) is a cytoskeletal protein, colocalizing with α-actinin on the Z line of mature muscle fibers. It plays a key role in dilated cardiomyopathy (DCM), muscular dystrophy, and tumor progression. However, correlations between PDLIM3 expression, prognosis, and tumor-infiltrating immune cells in gastric cancer are unknown. Therefore, we leveraged the Oncomine, GEPIA, GEO, and HPA databases to evaluate PDLIM3 expression in tumors. We also quantified PDLIM3 expression in 15 matched pairs of gastric tumor and nontumor tissues by immunohistochemistry. The Kaplan-Meier method was employed to determine the relationship between PDLIM3 expression and clinical outcomes. GO and KEGG analyses were performed to illuminate the molecular mechanisms of action of PDLIM3. TIMER2.0 and GEPIA were applied to investigate correlations between PDLIM3 expression and gene marker subsets signifying immune infiltration, with TIMER2.0 exploring the correlations between PDLIM3 and related signaling pathways. Gastric cancer tissues were found to express more PDLIM3 than nontumor tissues. PDLIM3 overexpression was associated with shorter OS and PFS of gastric cancer patients (OS HR = 2.02, P = 9.8e - 10; PFS HR = 1.77, P = 7.5e - 06). PDLIM3 was also positively correlated with worse OS and PFS according to gastric cancer staging, Her-2 overexpression, differentiation grade, and Lauren classification. PDLIM3 was shown to be associated with immunological responses by GO, while it was related to PI3K/Akt signal pathways by KEGG analysis. Furthermore, increased PDLIM3 expression was significantly correlated with greater infiltration of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. PDLIM3 expression had significant positive correlations with a variety of immune marker subsets. Finally, correlations were found between PDLIM3 and crucial markers of signaling pathways involving PI3K/Akt and p38 MAPK. Thus, upregulation of PDLIM3 was significantly associated with poor prognosis, immune cell infiltration, and activation of two key signal pathways in gastric cancer. We propose that PDLIM3 could be used as a biomarker to predict prognosis and immune cell infiltration in gastric cancer.
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Affiliation(s)
- Xinpeng Hu
- Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
| | - Minfeng Chen
- College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Qiang Ruan
- Department of The Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Changzheng Shi
- Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Engineering Research Center of Medical Imaging Artificial Intelligence for Precision Diagnosis and Treatment, Guangzhou 510630, China
| | - Jinghua Pan
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
| | - Liangping Luo
- Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
- Engineering Research Center of Medical Imaging Artificial Intelligence for Precision Diagnosis and Treatment, Guangzhou 510630, China
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Predicting peritoneal recurrence and disease-free survival from CT images in gastric cancer with multitask deep learning: a retrospective study. Lancet Digit Health 2022; 4:e340-e350. [DOI: 10.1016/s2589-7500(22)00040-1] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 12/14/2021] [Accepted: 02/10/2022] [Indexed: 12/24/2022]
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