Suzhen Fan1, Xiang Gao1, Qiaohong Qin1, Hongyu Li1, Zhongfu Yuan2, Shujun Zhao3. 1. Department of Obstetrics and Gynecology, Zhengzhou Key Laboratory of Gynecologic Oncology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. 2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. 3. Department of Obstetrics and Gynecology, Zhengzhou Key Laboratory of Gynecologic Oncology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: zhaoshujun0710@163.com.
Abstract
BACKGROUND: It remains unclear whether the tumor mutation burden (TMB) or a TMB-related signature could be prognostic indicators in ovarian cancer (OC), as potential correlations with immune infiltrates and immunotherapy responsiveness remains poorly understood. METHODS: Data of 941 OC patients were collected from three datasets, including 587, 260, and 94 patients from The Cancer Genome Atlas (TCGA), GSE32062, and the International Cancer Genome Consortium (ICGC), respectively. TMB was calculated and correlations with clinical outcomes, immune infiltrates, and immunotherapy responsiveness were investigated in the TCGA OC cohort. Weighted gene co-expression network analysis was performed to identify TMB-related genes. A TMB-related signature was constructed and validated. RESULTS: Higher TMB was associated with better survival in the TCGA and ICGC OC cohorts. The high-TMB group had higher CD8+ T-cell infiltration than the low-TMB group. No significant correlation was found between TMB and immunotherapy response. Furthermore, we selected 8 prognostic and TMB-related genes to construct a TMB-related signature that could distinguish between the high- and low-risk patients; its predictive power was validated in the GSE32062 and ICGC datasets. SubMap analysis suggested that patients in the low-risk group might have a better response to anti-PD1 therapy. CONCLUSIONS: We examined the prognostic value of TMB and its potential association with immune cell infiltration and immunotherapy responsiveness in OC. A TMB-related prognostic signature consisting of 8 genes was developed and verified, which might be a promising prognostic signature for the prognosis of OC patients.
BACKGROUND: It remains unclear whether the tumor mutation burden (TMB) or a TMB-related signature could be prognostic indicators in ovarian cancer (OC), as potential correlations with immune infiltrates and immunotherapy responsiveness remains poorly understood. METHODS: Data of 941 OC patients were collected from three datasets, including 587, 260, and 94 patients from The Cancer Genome Atlas (TCGA), GSE32062, and the International Cancer Genome Consortium (ICGC), respectively. TMB was calculated and correlations with clinical outcomes, immune infiltrates, and immunotherapy responsiveness were investigated in the TCGA OC cohort. Weighted gene co-expression network analysis was performed to identify TMB-related genes. A TMB-related signature was constructed and validated. RESULTS: Higher TMB was associated with better survival in the TCGA and ICGC OC cohorts. The high-TMB group had higher CD8+ T-cell infiltration than the low-TMB group. No significant correlation was found between TMB and immunotherapy response. Furthermore, we selected 8 prognostic and TMB-related genes to construct a TMB-related signature that could distinguish between the high- and low-risk patients; its predictive power was validated in the GSE32062 and ICGC datasets. SubMap analysis suggested that patients in the low-risk group might have a better response to anti-PD1 therapy. CONCLUSIONS: We examined the prognostic value of TMB and its potential association with immune cell infiltration and immunotherapy responsiveness in OC. A TMB-related prognostic signature consisting of 8 genes was developed and verified, which might be a promising prognostic signature for the prognosis of OC patients.