A Novel DNA Repair Gene Signature for Immune Checkpoint Inhibitor-Based Therapy in Gastric Cancer

Journal Article · 23 May 2022 · Frontiers in Cell and Developmental Biology

DOI: https://doi.org/10.3389/fcell.2022.893546 · OSTI ID:1896676

Yuan, Binbin ^[1]; Jiang, Chengfei ^[1]; Chen, Lingyan ^[1]; Wen, Lihui ^[1]; Cui, Jinlong ^[2]; Chen, Min ^[1]; Zhang, Shu ^[1]; Zhou, Lin ^[1]; Cai, Yimeng ^[3]; Mao, Jian-Hua ^[4]; Zou, Xiaoping ^[1]; Hang, Bo ^[4]; Wang, Pin ^[1]

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1. Nanjing Univ. (China)
2. Berkeley-Nanjing Research Center, Nanjing (China)
3. Univ. of California, Berkeley, CA (United States)
4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER)
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 1896676
• Journal Information: Frontiers in Cell and Developmental Biology, Vol. 10; ISSN 2296-634X
• Publisher: Frontiers Media S.A.Copyright Statement
• Country of Publication: United States
• Language: English