肿瘤科
队列
免疫疗法
免疫检查点
医学
基因突变
癌症
癌症研究
基因
DNA修复
突变
生物标志物
内科学
生物
遗传学
作者
Yujiao Wang,Xi Ji,Shuang Li,Huan Chen,Xin Wei,Chang Liu,Jifang Gong,Xiaotian Zhang,Xicheng Wang,Zhi Peng,Changsong Qi,Zhenghang Wang,Yanni Wang,Na Zhuo,Jianling Zou,Henghui Zhang,Jian Li,Lin Shen,Zhihao Lü
标识
DOI:10.20892/j.issn.2095-3941.2020.0708
摘要
Immune checkpoint inhibitors (ICIs) have achieved remarkable results in cancer treatments. However, there is no effective predictive biomarker for gastrointestinal (GI) cancer.We conducted integrative analyses of the genomic and survival data of ICI-treated GI cancer patients from the Memorial Sloan Kettering Cancer Center cohort (MSK-GI, n = 227), the Janjigian cohort (n = 40), and the Peking University Cancer Hospital & Institute cohort (PUCH, n = 80) to determine the possible associations between DNA damage response and repair (DDR) gene mutations and clinical outcomes. Data from The Cancer Genome Atlas database were analyzed to determine the possible correlations between DDR gene mutations and the tumor microenvironment.In the MSK cohort, the presence of ≥ 2 DDR gene mutations was correlated with prolonged overall survival (OS). The Janjigian and PUCH cohorts further confirmed that subgroups with ≥ 2 DDR gene mutations displayed a prolonged OS and a higher durable clinical benefit. Furthermore, the DDR gene mutation load could be considered as an independent prognostic factor, and exhibited a potential predictive value for survival in GI cancer patients treated with ICIs. Mechanistically, we showed that the presence of ≥ 2 DDR gene mutations was correlated with higher levels of tumor mutation burden, neoantigen, and T cell infiltration.The DDR gene mutation status was correlated with favorable clinical outcomes in GI cancer patients receiving ICIs, which could serve as a potential biomarker to guide patient selection for immunotherapy.
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