Open AccessAssociation between DNA damage repair gene somatic mutations and immune‐related gene expression in ovarian cancer
Author(s) -
Tian Wenjuan,
Shan Boer,
Zhang Yuzi,
Ren Yulan,
Liang Shanhui,
Zhao Jing,
Zhao Zhengyi,
Wang Guoqiang,
Zhao Xiaochen,
Peng Dongxian,
Bi Rui,
Cai Shangli,
Bai Yuezong,
Wang Huaying
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2849
Subject(s) - immune system , germline mutation , immunotherapy , ovarian cancer , cancer , mutation , immunology , genome instability , medicine , cancer research , biology , gene , dna damage , genetics , dna
Background Defects in DNA damage repair (DDR) system may lead to genomic instability and manifest as increased immunogenicity. DDR deficiency is prevalent in ovarian cancer (OvCa); however, the association of DDR mutation with immune profiles in OvCa remains largely unknown. This knowledge will provide an essential basis to the rational design of biomarker‐guided immune combination therapy of OvCa in the future. Methods Whole‐exome sequencing data of 587 OvCa from The Cancer Genome Atlas (TCGA) were used to determine the expression profiles of 47 immune‐related genes and the abundance of tumor‐infiltrating immune cells. A Chinese OvCa cohort (n = 220) tested by next‐generation sequencing (NGS) was used to validate the association between DDR status and tumor mutation burden (TMB). Results A total of 19.3% in TCGA cohort and 25.9% in Chinese cohort harbored at least one DDR somatic mutation. DDR deficiency exhibited a distinct immune profile with significant higher expression levels of PTPRCAP, CCL5, IFI16, LAG3, IL15RA, and GBP1 in OvCa in the TCGA cohort. Different DDR pathway deficiency displayed various immune profiles. Increased levels of Th1 cells, TMB, and neoantigen were also observed in DDR‐deficient tumors. Conclusions DDR deficiency was associated with specific immune signatures in OvCa. Our findings emphasize the urgent need for biomarker‐guided rational immune combination therapy to maximize the OvCa patients who could benefit from immunotherapy.