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. 2020 Jan 1;11(4):776-780.
doi: 10.7150/jca.41296. eCollection 2020.

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

Tao Jiang  1   2   3 , Xiaoxia Chen  1   3 , Chunxia Su  1   3 , Shengxiang Ren  1 , Caicun Zhou  1
Affiliations

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

Tao Jiang et al. J Cancer. .

Abstract

ARID1A 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 ARID1A 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 ARID1A alterations across >40,000 cases in multiple cancer types. We found a high frequency (6.2%) of ARID1A, which were associated with significantly higher tumor mutation burden level across various cancers. Importantly, patients with ARID1A 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, ARID1A alterations were correlated with markedly high immune infiltrates in endometrial, stomach and colon cancer. However, patients with ARID1A-mutant renal clear cell carcinoma had dramatically lower CD8+ T cell infiltrations than those without, indicating the association between ARID1A alterations and immune infiltrates was cancer-dependent. Collectively, our findings highlight the important value of ARID1A alterations as pan-cancer predictive biomarkers for ICI treatment.

Keywords: ARID1A; Biomarker; Immunotherapy; Pan-cancer..

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Genetic alterations of ARID1A and its association with TMB level. A. Prevalence of ARID1A alterations in different cancer types; B. Co-occurring of genetic mutations in cancers with ARID1A alterations; C. The association between TMB and ARID1A mutations in MSK-IMPACT cohort; D. The association between TMB and ARID1A alterations in immune checkpoint inhibitors treatment cohort; E. The association between TMB and ARID1A alterations in patients with microsatellite-stable solid tumors received immune checkpoint inhibitors treatment. TMB, tumor mutation burden; Mut, mutation; WT, wild type.
Figure 2
Figure 2
Predictive and prognostic value of ARID1A alterations. A. Predictive value of ARID1A alterations in all cancers; B. Prognostic value of ARID1A alterations in all cancers; C. Predictive value of ARID1A alterations in patients received ICI therapy; D. Subgroup analysis the predictive value of ARID1A alterations subtypes in patients received ICI treatment. Mut, mutation; WT, wild type.
Figure 3
Figure 3
Immune landscape of cancer with ARID1A alterations. The association between ARID1A alterations and six immune infiltrates in A. Endometrial cancer; B. Stomach carcinoma; C. Colon adenocarcinoma; D. Renal clear cell carcinoma.
See this image and copyright information in PMC

References

    1. Sacher AG, Gandhi L. Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer: A Review. JAMA Oncol. 2016;2(9):1217–1222. - PubMed
    1. Keenan TE, Burke KP, Van Allen EM. Genomic correlates of response to immune checkpoint blockade. Nat Med. 2019;25(3):389–402. - PMC - PubMed
    1. Miao D, Margolis CA, Vokes NI, Liu D, Taylor-Weiner A, Wankowicz SM, Adeegbe D, Keliher D, Schilling B, Tracy A. et al. Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet. 2018;50(9):1271–1281. - PMC - PubMed
    1. Wu JN, Roberts CW. ARID1A mutations in cancer: another epigenetic tumor suppressor? Cancer Discov. 2013;3(1):35–43. - PMC - PubMed
    1. Karachaliou N, Paulina Bracht JW, Rosell R. ARID1A Gene Driver Mutations in Lung Adenocarcinomas. J Thorac Oncol. 2018;13(12):e255–e257. - PubMed