SMARCA4alterations in non-small cell lung cancer: a systematic review and meta-analysis

Abstract

AimsA mutation in theSMARCA4gene which encodes BRG1, a common catalytic subunit of switch/sucrose non-fermentable chromatin-remodelling complexes, plays a vital role in carcinogenesis.SMARCA4mutations are present in approximately 10% of non-small cell lung cancers (NSCLC), making it a crucial gene in NSCLC, but with varying prognostic associations. To explore this, we conducted a systematic review and meta-analysis on the prognostic significance ofSMARCA4mutations in NSCLC.MethodsElectronic database search was performed from inception to December 2022. Study characteristics and prognostic data were extracted from each eligible study. Depending on heterogeneity, pooled HR and 95% CI were derived using the random-effects or fixed-effects models.Results8 studies (11 cohorts) enrolling 8371 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 8 (10 cohorts) and 1 (3 cohorts) studies, respectively. ComparingSMARCA4-mutated NSCLC patients withSMARCA4-wild-type NSCLC patients, the summary HRs for OS and PFS were 1.49 (95% CI 1.18 to 1.87; I2=84%) and 3.97 (95% CI 1.32 to 11.92; I2=79%), respectively. The results from the trim-and-fill method for publication bias and sensitivity analysis were inconsistent with the primary analyses. Three studies reported NSCLC prognosis for category I and II mutations separately; category I was significantly associated with OS.ConclusionOur findings suggest thatSMARCA4mutation negatively affects NSCLC OS and PFS. The prognostic effects ofSMARCA4-co-occurring mutations and the predictive role ofSMARCA4mutation status in immunotherapy require further exploration.