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Genetic alterations and expression characteristics of ARID1A impact tumor immune contexture and survival in early-onset gastric cancer

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Oncol, Tongji Med Coll, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Inst Pathol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China [3]Huazhong Univ Sci & Technol, Union Hosp, Dept Gastrointestinal Surg, Tongji Med Coll, Wuhan 430030, Peoples R China [4]Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, 1515 Holcombe Blvd, Houston, TX 77030 USA [5]Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA [6]Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA [7]Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Ophthalmol, Sch Med, Shanghai 200025, Peoples R China [8]Wuhan Iron & Steel Grp Corp, Dept Oncol, Hosp 2, Wuhan 430080, Peoples R China [9]Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Cell Dev & Canc Biol, Portland, OR 97201 USA
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关键词: ARID1A target sequencing early-onset gastric cancer heterogeneity tumor immune contexture

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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.

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基金编号: P30 CA016672

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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出版当年[2018]版:
Q2 ONCOLOGY
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Q2 ONCOLOGY

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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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