Subunits of ARID1 serve as novel biomarkers for the sensitivity to immune checkpoint inhibitors and prognosis of advanced non-small cell lung cancer.

Abstract

Introduction Patients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with immune checkpoint inhibitors (ICIs). Biomarkers such as programmed death-ligand 1 (PD-L1), the tumor mutational burden (TMB) and the mismatch repair (MMR) status are used to predict the prognosis of ICIs therapy. Nevertheless, novel biomarkers need to be further investigated, and a systematic prognostic model is needed for the evaluation of the survival risks of ICIs treatment.Methods A cohort of 240 patients who received ICIs from the cBioPortal for Cancer Genomics was evaluated in this research. Clinical information and targeted sequencing data were acquired for analyses. The Kaplan-Meier plot method was used to perform survival analyses, and selected variables were then confirmed by a novel nomogram constructed by the “rms” package of R software.Results Seven percent of the NSCLC patients harbored ARID1A mutations, while 4% of the NSCLC patients harbored ARID1B mutations. Mutations in ARID1A and ARID1B were confirmed to be associated with sensitivity to ICIs. Patients harboring these mutations were found to have a better response to treatment (ARID1A: P=0.045; ARID1B: P=0.034) and prolonged progression-free survival (ARID1B: P=0.032). Here, a novel nomogram was constructed to predict the prognosis of ICIs treatment. Elevation of the TMB, enhanced expression of PD-L1 and activation of the antigen presentation process and cellular immunity were found to be correlated with ARID1A and ARID1B mutations.Conclusion ARID1A and ARID1B could serve as novel biomarkers for the prognosis and sensitivity to ICIs of advanced NSCLC.

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“…In addition, available data revealed that the role of ARID1A in predicting the efficacy of ICI therapy remains controversial. [41,42] In this study, patients with mutated FGF pathway had numerically longer survival than those with unaltered pathway. Aberrant FGF signaling pathway was reported to be associated with indolent behavior and favorable prognosis in patients with BTCs.…”

“…Patients with ARID1B mutations had longer PFS and OS, which was consistent with findings by Zhu et al40 In contrast, patients harboring ARID1A mutations seemed to have poorer survival, which is inconclusive because of the small sample size ( n = 4). In addition, available data revealed that the role of ARID1A in predicting the efficacy of ICI therapy remains controversial 41,42. In this study, patients with mutated FGF pathway had numerically longer survival than those with unaltered pathway.…”