RT Journal Article
SR Electronic
T1 Alterations in DNA damage response and repair genes as potential biomarkers for immune checkpoint blockade in gastrointestinal cancer
JF Cancer Biology & Medicine
JO Cancer Biology & Medicine
FD China Anti-Cancer Association
SP 1139
OP 1149
DO 10.20892/j.issn.2095-3941.2020.0708
VO 19
IS 8
A1 Wang, Yujiao
A1 Jiao, Xi
A1 Li, Shuang
A1 Chen, Huan
A1 Wei, Xin
A1 Liu, Chang
A1 Gong, Jifang
A1 Zhang, Xiaotian
A1 Wang, Xicheng
A1 Peng, Zhi
A1 Qi, Changsong
A1 Wang, Zhenghang
A1 Wang, Yanni
A1 Zhuo, Na
A1 Zou, Jianling
A1 Zhang, Henghui
A1 Li, Jian
A1 Shen, Lin
A1 Lu, Zhihao
YR 2022
UL http://www.cancerbiomed.org/content/19/8/1139.abstract
AB Objective: Immune checkpoint inhibitors (ICIs) have achieved remarkable results in cancer treatments. However, there is no effective predictive biomarker for gastrointestinal (GI) cancer.Methods: 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.Results: 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.Conclusions: 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.