A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis
Background: The prognostic significance of immune checkpoint expression in the tumor microenvironment has been widely investigated in colorectal cancers. However, the results of these studies are inconsistent and limited to some immune checkpoints. Objective: The study aimed to investigate the corre...
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Elsevier
2024-01-01
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| Series: | Current Therapeutic Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0011393X24000304 |
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| author | Mahdieh Azizi, PhD Zahra Mokhtari, MSc Shirin Tavana, MSc Peyman Bemani, PhD Zahra Heidari, PhD Roghayeh Ghazavi, PhD Marzieh Rezaei, PhD |
| author_facet | Mahdieh Azizi, PhD Zahra Mokhtari, MSc Shirin Tavana, MSc Peyman Bemani, PhD Zahra Heidari, PhD Roghayeh Ghazavi, PhD Marzieh Rezaei, PhD |
| author_sort | Mahdieh Azizi, PhD |
| collection | DOAJ |
| description | Background: The prognostic significance of immune checkpoint expression in the tumor microenvironment has been widely investigated in colorectal cancers. However, the results of these studies are inconsistent and limited to some immune checkpoints. Objective: The study aimed to investigate the correlation between different immune checkpoint expression and clinicopathological features and prognostic parameters. Methods: We conducted a systematic review and meta-analysis of the published literature in PubMed, Web of Science-Core Collection, Scopus, Embase, and Cochrane databases to summarize the association between various immune checkpoints expression on both tumor cells and immune cells with clinicopathological features and prognostic parameters in patients with colorectal cancer. Results: One hundred four studies incorporating 22,939 patients were included in our meta-analysis. Our results showed that among the B7 family, the high expression of B7H3, B7H4, PD-1, and PD-L1 on tumor cells and tumor tissue was significantly associated with higher T stage, advanced tumor, node, metastasis (TNM) stage, presence of vascular invasion, and lymphatic invasion. In addition, patients with high expression of B7H3, B7H4, PD-1, PD-L1, and PD-L2 were associated with shorter overall survival. High expression of PD-1 and PD-L1 in immune cells correlated with the absence of lymph node metastasis, lower TNM stage, early T stage, poor overall survival, and disease-free survival, respectively. Moreover, we found significant positive correlations between CD70 and Galectin-3 expression with advanced T stage. HLA-II overexpression was correlated with the absence of lymph node metastasis (odds ratio = 0.21, 95% CI = 0.11–0.38, P < 0.001) and early TNM stage (odds ratio = 0.35, 95% CI = 0.26–0.47, P < 0.001). Conclusions: Overexpression of B7H3, B7H4, PD-1, PD-L1, PD-L2, CD70, and Galectin-3 on tumors is significantly associated with unfavorable clinicopathological characteristics and poor prognostic factors. Hence, these immune checkpoints can serve as predictive biomarkers for prognosis and the clinicopathological features of colorectal cancer because this is essential to identify patients suitable for anticancer therapy with immune checkpoint inhibitors. |
| format | Article |
| id | doaj-art-176d6276dfa4420aae4c794f7dbc8956 |
| institution | OA Journals |
| issn | 0011-393X |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
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| series | Current Therapeutic Research |
| spelling | doaj-art-176d6276dfa4420aae4c794f7dbc89562025-08-20T02:35:37ZengElsevierCurrent Therapeutic Research0011-393X2024-01-0110110076010.1016/j.curtheres.2024.100760A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-AnalysisMahdieh Azizi, PhD0Zahra Mokhtari, MSc1Shirin Tavana, MSc2Peyman Bemani, PhD3Zahra Heidari, PhD4Roghayeh Ghazavi, PhD5Marzieh Rezaei, PhD6Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Biostatistics and Epidemiology, Faculty of Health, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Knowledge and Information Science, Faculty of Education and Psychology, Shahid Chamran University of Ahvaz, Ahvaz, IranDepartment of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Address correspondence to: Marzieh Rezaei, Ph.D, Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Hezar Jarib Street, Postal Code 8174673461, Isfahan, Iran.Background: The prognostic significance of immune checkpoint expression in the tumor microenvironment has been widely investigated in colorectal cancers. However, the results of these studies are inconsistent and limited to some immune checkpoints. Objective: The study aimed to investigate the correlation between different immune checkpoint expression and clinicopathological features and prognostic parameters. Methods: We conducted a systematic review and meta-analysis of the published literature in PubMed, Web of Science-Core Collection, Scopus, Embase, and Cochrane databases to summarize the association between various immune checkpoints expression on both tumor cells and immune cells with clinicopathological features and prognostic parameters in patients with colorectal cancer. Results: One hundred four studies incorporating 22,939 patients were included in our meta-analysis. Our results showed that among the B7 family, the high expression of B7H3, B7H4, PD-1, and PD-L1 on tumor cells and tumor tissue was significantly associated with higher T stage, advanced tumor, node, metastasis (TNM) stage, presence of vascular invasion, and lymphatic invasion. In addition, patients with high expression of B7H3, B7H4, PD-1, PD-L1, and PD-L2 were associated with shorter overall survival. High expression of PD-1 and PD-L1 in immune cells correlated with the absence of lymph node metastasis, lower TNM stage, early T stage, poor overall survival, and disease-free survival, respectively. Moreover, we found significant positive correlations between CD70 and Galectin-3 expression with advanced T stage. HLA-II overexpression was correlated with the absence of lymph node metastasis (odds ratio = 0.21, 95% CI = 0.11–0.38, P < 0.001) and early TNM stage (odds ratio = 0.35, 95% CI = 0.26–0.47, P < 0.001). Conclusions: Overexpression of B7H3, B7H4, PD-1, PD-L1, PD-L2, CD70, and Galectin-3 on tumors is significantly associated with unfavorable clinicopathological characteristics and poor prognostic factors. Hence, these immune checkpoints can serve as predictive biomarkers for prognosis and the clinicopathological features of colorectal cancer because this is essential to identify patients suitable for anticancer therapy with immune checkpoint inhibitors.http://www.sciencedirect.com/science/article/pii/S0011393X24000304colorectal cancerimmune checkpointsimmunotherapymeta-analysisprognostic biomarkertumor microenvironment |
| spellingShingle | Mahdieh Azizi, PhD Zahra Mokhtari, MSc Shirin Tavana, MSc Peyman Bemani, PhD Zahra Heidari, PhD Roghayeh Ghazavi, PhD Marzieh Rezaei, PhD A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis Current Therapeutic Research colorectal cancer immune checkpoints immunotherapy meta-analysis prognostic biomarker tumor microenvironment |
| title | A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis |
| title_full | A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis |
| title_fullStr | A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis |
| title_short | A Comprehensive Study on the Prognostic Value and Clinicopathological Significance of Different Immune Checkpoints in Patients With Colorectal Cancer: A Systematic Review and Meta-Analysis |
| title_sort | comprehensive study on the prognostic value and clinicopathological significance of different immune checkpoints in patients with colorectal cancer a systematic review and meta analysis |
| topic | colorectal cancer immune checkpoints immunotherapy meta-analysis prognostic biomarker tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S0011393X24000304 |
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