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The Somatic Mutational Landscape and Role of ARID1A Gene in Hepatocellular Carcinoma

SSRN Electronic Journal
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  • Usage
    276
    • Abstract Views
      239
    • Downloads
      37

Article Description

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Describing the somatic mutational landscape of important genes can contribute to identifying new therapeutic targets and performing individualized therapeutic approaches for HCC patients. The mutation and expression change of ARID1A gene in HCC remain unclear. Methods: cBioPortal was used to visualize genetic alterations of ARID1A mutations and DNA copy-number alterations (CNAs). The influence of ARID1A mutation for HCC patients overall survival (OS) was also determined. Then, a meta-analysis was further conducted to verify the relationship between ARID1A mutations or expression and HCC patients prognosis. Besides, TIMER 2.0 and The Cancer Genome Atlas databases were used to analyze the correlations between ARID1A expression and cancer immune infiltrates. Results: We found that ARID1A mutations were frequently shown in 9.83% (36/366) sequenced HCC cases, and ARID1A mutation resulted in decreased expression of ARID1A mRNA. Patients with ARID1A mutation or low expression had worse OS (HR = 2.01; 95% CI = 1.61–2.50) and RFS (HR = 1.30; 95% CI = 1.06–3.1.59) than non-mutation or high group in HCC, and low ARID1A expression was correlated with tumor size. More importantly, our data also demonstrated that the ARID1A expression was correlated with tumor mutational burden (TMB) and high immune cell infiltration in the ARID1A low expression group. Further analysis showed that the ARID1A expression in HCC samples was related to macrophage polarization. Conclusions: ARID1A mutation or expression can be considered as a potential prognostic biomarker as well as an immunotherapy modulator for HCC patients. Funding Information: This work was supported by the grants from the Taishan Scholars Program for Young Expert of Shandong Province (Grant No. tsqn20161064), National Natural Science Foundation of China (Grant No. 82073200, 82172647 & 81874178), Funds for Independent Cultivation of Innovative Team from Universities in Jinan (Grant No. 2020GXRC023), Shandong Provincial Natural Science Foundation (Grant No. ZR202105070027, ZR2021MH194) and China Postdoctoral Science Foundation (2020M682192). Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Bibliographic Details

Guang-Xiao Meng; Chun-Cheng Yang; Lun-Jie Yan; Ya-Fei Yang; Yu-Chuang Yan; Jian-Guo Hong; Zhi-Qiang Chen; Zhao-Ru Dong; Tao Li

Elsevier BV

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