The AT-rich Interactive Domain 1A (ARID1A) is one of the most frequently mutated genes in gastric cancer. Here, we found that genetic variants in noncoding regions of ARID1A associated with altered protein levels by target sequencing. Notably, tumors with ARID1A variants in the 3'untranslated region (3'UTR) exhibited remarkably increased heterogeneity of ARID1A protein. In general, genetic variants and protein deficiency of ARID1A in tumors were associated with a better survival. Strikingly, altered patterns and heterogeneity of ARID1A protein expression were observed in peritumor tissues and carried significant implications in defining tumor immune contexture by multiplex immunohistochemistry. By analyzing the spatial distribution of TILs, we showed that reduced ARID1A protein levels in both tumor and peritumor tissues were significantly correlated with increased density and proximity of TILs to tumor cells. In contrast, high heterogeneity of ARID1A expression was associated with increased TIL density, but reduced proximity of TILs to tumor cells. Collectively, our study characterized ARID1A genetic alterations and its protein expression patterns in EOGC, demonstrating new strategies for clinically assessing its molecular impact on tumor onset and progression, tumor immune response, and patient survival.
基金:
NCI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA016672] Funding Source: Medline
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Oncol, Tongji Med Coll, Wuhan 430030, Peoples R China
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推荐引用方式(GB/T 7714):
zou jun,qin wan,yang lin,et al.Genetic alterations and expression characteristics of ARID1A impact tumor immune contexture and survival in early-onset gastric cancer[J].AMERICAN JOURNAL OF CANCER RESEARCH.2020,10(11):3947-+.
APA:
zou,jun,qin,wan,yang,lin,wang,lulu,wang,yu...&peng,guang.(2020).Genetic alterations and expression characteristics of ARID1A impact tumor immune contexture and survival in early-onset gastric cancer.AMERICAN JOURNAL OF CANCER RESEARCH,10,(11)
MLA:
zou,jun,et al."Genetic alterations and expression characteristics of ARID1A impact tumor immune contexture and survival in early-onset gastric cancer".AMERICAN JOURNAL OF CANCER RESEARCH 10..11(2020):3947-+