Yuan Gao1, Yu Xu2,3, Meiqin Gao2,3, Aimin Huang2,3, Pan Chi1. 1. Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China. 2. Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China. 3. Institute of Oncology of Fujian Medical University, Fuzhou, China.
Abstract
BACKGROUND: There have been inconsistent results and conflicting conclusions among the existing prognostic studies of B7-H3 expression in colon cancer patients. Therefore, the association between B7-H3 expression and colon cancer survival has remained largely unclear. METHODS: We performed a three-phase and trans-ethnic prognostic study of B7-H3 expression in colon cancer patients involving perhaps the largest population to date. In the discovery phase, we utilized a Cox proportional hazards model adjusted for covariates to test the association between B7-H3 expression and colon cancer overall survival (OS) time in a European population from The Cancer Genome Atlas (TCGA) cohort (n=433). In the validation phase I, the association was replicated in a European population from Gene Expression Omnibus (GEO) cohort (n=811). In the validation phase II, we again confirmed the significant association in an Asian population from Fujian Medical University Union Hospital (UNION) cohort (n=179). Furthermore, a series of Kaplan-Meier analysis, bioinformatics analysis of tumor immune microenvironment (TIME), and immune checkpoint prognostic prediction analysis, as well as sensitivity analysis, were also conducted. RESULTS: Highly expressed B7-H3 was a significant and robust biomarker to colon cancer survival, with a large hazard ratio (HR) [HRTCGA =4.60, 95% confidence interval (CI): 2.15 to 9.83, P=8.37×10-05; HRGEO =1.47, 95% CI: 1.12 to 1.94, P=0.0056; HRUNION =1.63, 95% CI: 1.36 to 1.95, P=7.91×10-08]. We detected an involvement of B7-H3 in the tumor immune microenvironment (TIME). Meanwhile, B7-H3 was significantly and weakly correlated with 6 out of 27 well-recognized immune checkpoint genes. Even after adjusting for effects of other immune checkpoint genes, B7-H3 still exhibited a harmful effect on colon cancer survival using samples from TCGA and GEO cohorts (HR =1.47, 95% CI: 1.07 to 2.02, P=0.0184), indicating that it was an independent prognostic factor of colon cancer. We also proposed an immune checkpoint prognostic risk score which possessed the capability to identify colon cancers with high risk of mortality. CONCLUSIONS: The expression of B7-H3 is a significant, robust, and independent prognostic factor to colon cancer OS. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: There have been inconsistent results and conflicting conclusions among the existing prognostic studies of B7-H3 expression in colon cancer patients. Therefore, the association between B7-H3 expression and colon cancer survival has remained largely unclear. METHODS: We performed a three-phase and trans-ethnic prognostic study of B7-H3 expression in colon cancer patients involving perhaps the largest population to date. In the discovery phase, we utilized a Cox proportional hazards model adjusted for covariates to test the association between B7-H3 expression and colon cancer overall survival (OS) time in a European population from The Cancer Genome Atlas (TCGA) cohort (n=433). In the validation phase I, the association was replicated in a European population from Gene Expression Omnibus (GEO) cohort (n=811). In the validation phase II, we again confirmed the significant association in an Asian population from Fujian Medical University Union Hospital (UNION) cohort (n=179). Furthermore, a series of Kaplan-Meier analysis, bioinformatics analysis of tumor immune microenvironment (TIME), and immune checkpoint prognostic prediction analysis, as well as sensitivity analysis, were also conducted. RESULTS: Highly expressed B7-H3 was a significant and robust biomarker to colon cancer survival, with a large hazard ratio (HR) [HRTCGA =4.60, 95% confidence interval (CI): 2.15 to 9.83, P=8.37×10-05; HRGEO =1.47, 95% CI: 1.12 to 1.94, P=0.0056; HRUNION =1.63, 95% CI: 1.36 to 1.95, P=7.91×10-08]. We detected an involvement of B7-H3 in the tumor immune microenvironment (TIME). Meanwhile, B7-H3 was significantly and weakly correlated with 6 out of 27 well-recognized immune checkpoint genes. Even after adjusting for effects of other immune checkpoint genes, B7-H3 still exhibited a harmful effect on colon cancer survival using samples from TCGA and GEO cohorts (HR =1.47, 95% CI: 1.07 to 2.02, P=0.0184), indicating that it was an independent prognostic factor of colon cancer. We also proposed an immune checkpoint prognostic risk score which possessed the capability to identify colon cancers with high risk of mortality. CONCLUSIONS: The expression of B7-H3 is a significant, robust, and independent prognostic factor to colon cancer OS. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
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