机构：[1]Department of Radiation Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China,[2]Institute of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, China,昆明医科大学附属第一医院[3]Medical Department,Genecast Biotechnology Co., Ltd, Wuxi, China,[4]Center of Integrative Medicine, Beijing Ditan Hospital, Capital MedicalUniversity, Beijing, China,[5]Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China,[6]Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China,[7]Department of Oncology,Sichuan Provincial People’s Hospital, Chengdu, China四川省人民医院
Background DNA damage repair (DDR) genes were recently implicated in the anti-tumor immune response. Therefore, it is worthwhile to unravel the implications of DDR pathways in the shaping of immune responsiveness in colorectal cancer (CRC) patients receiving immune checkpoint inhibitors (ICI). Methods We analyzed publicly available genomic data from a cohort treated with ICI from Memorial Sloan Kettering Cancer Center (MSK ICI cohort). To characterize the impact of the DDR mutation, the genomic data of The Cancer Genome Atlas (TCGA) colorectal adenocarcinoma (COADREAD) dataset was explored. We also analyzed the incidence of DDR mutation and microsatellite instability-high (MSI-H) in a Chinese CRC cohort using panel sequencing. Results The DDR pathway was commonly mutated (21.8%) in the multicancer MSK ICI cohort, with the highest frequency of 36.4% in CRCs. Survival analysis showed that DDR mutation correlated with an improved overall survival (OS) in CRCs and pan-cancer in the MSK ICI cohort. However, no significant associations were identified in the TCGA COADREAD and MSK non-ICI CRCs. DDR mutation was associated with higher tumor mutational burden (TMB) levels and increased immune cell infiltration and immune checkpoint molecule expression in the TCGA COADREAD dataset. Last, we investigated the DDR mutational pattern and its associations with MSI-H and other genomic features in a Chinese CRC cohort. Notably, MSI-H and DDR mutation was present in 5.7% and 13.4% of cases, respectively, which suggests that DDR identifies a higher proportion of potential responders than MSI-H. Conclusion Our data suggest that DDR mutation as an indication of enhanced cancer immunity, and it may function as a biomarker for patients with CRCs receiving ICI treatment. The high incidence of DDR mutation in the Chinese CRC cohort emphasizes the future utility of panel-based DDR evaluation in guiding ICI treatment.
基金：
General Project of Yunnan Provincial Science and Technology Department [2019FB114]
第一作者机构：[1]Department of Radiation Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China,
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Song Yipeng,Huang Jian,Liang Dandan,et al.DNA Damage Repair Gene Mutations Are Indicative of a Favorable Prognosis in Colorectal Cancer Treated With Immune Checkpoint Inhibitors[J].FRONTIERS IN ONCOLOGY.2021,10:doi:10.3389/fonc.2020.549777.
APA：
Song, Yipeng,Huang, Jian,Liang, Dandan,Hu, Ying,Mao, Beibei...&Zhang, Shukun.(2021).DNA Damage Repair Gene Mutations Are Indicative of a Favorable Prognosis in Colorectal Cancer Treated With Immune Checkpoint Inhibitors.FRONTIERS IN ONCOLOGY,10,
MLA：
Song, Yipeng,et al."DNA Damage Repair Gene Mutations Are Indicative of a Favorable Prognosis in Colorectal Cancer Treated With Immune Checkpoint Inhibitors".FRONTIERS IN ONCOLOGY 10.(2021)
