SMARCA4 alterations in non-small cell lung cancer: a systematic review and meta-analysis.

AIMS: A mutation in the SMARCA4 gene which encodes BRG1, a common catalytic subunit of switch/sucrose non-fermentable chromatin-remodelling complexes, plays a vital role in carcinogenesis. SMARCA4 mutations 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 of SMARCA4 mutations in NSCLC.

METHODS: Electronic 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.

RESULTS: 8 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. Comparing SMARCA4 -mutated NSCLC patients with SMARCA4 -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.

CONCLUSION: Our findings suggest that SMARCA4 mutation negatively affects NSCLC OS and PFS. The prognostic effects of SMARCA4 -co-occurring mutations and the predictive role of SMARCA4 mutation status in immunotherapy require further exploration.