Pan-cancer analysis of ARID1A Alterations as Biomarkers for Immunotherapy Outcomes

• Published in: Journal of Cancer Vol. 11; no. 4; pp. 776 - 780
• Main Authors: Jiang, Tao, Chen, Xiaoxia, Su, Chunxia, Ren, Shengxiang, Zhou, Caicun
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2020; Ivyspring International Publisher
• Subjects: Antigens; Apoptosis; Biomarkers; Colon; Confidence intervals; Cytotoxicity; Endometrial cancer; Ligands; Lymphocytes; Mutation; Online data bases; Proteins; Research Paper; Tumors; Biomarker; ARID1A; Pan-cancer; Immunotherapy
• ISSN: 1837-9664; 1837-9664
• DOI: 10.7150/jca.41296

alterations would compromise mismatch repair pathway and increase the number of tumor-infiltrating lymphocytes and PD-L1 expression in some cancers, which would cooperate with immune checkpoint inhibitors (ICIs) treatment. However, a comprehensive analysis of
alteration frequency and its predictive value for ICI treatment outcome in cancers has not yet been investigated. Hence, we performed this pan-cancer analysis to evaluate the prevalence and predictive value of
alterations across >40,000 cases in multiple cancer types. We found a high frequency (6.2%) of
, which were associated with significantly higher tumor mutation burden level across various cancers. Importantly, patients with
alterations and advanced cancers had the substantially prolonged overall survival in ICI treatment cohort, suggesting it might be used to predict a survival benefit from ICI therapy across multiple cancer types. Notably,
alterations were correlated with markedly high immune infiltrates in endometrial, stomach and colon cancer. However, patients with
-mutant renal clear cell carcinoma had dramatically lower CD8
T cell infiltrations than those without, indicating the association between
alterations and immune infiltrates was cancer-dependent. Collectively, our findings highlight the important value of
alterations as pan-cancer predictive biomarkers for ICI treatment.