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

J Clin Pathol. 2024 Jun 19;77(7):457-463. doi: 10.1136/jcp-2024-209394.

Abstract

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.

Keywords: Lung Neoplasms; ONCOGENES.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • DNA Helicases* / analysis
  • DNA Helicases* / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Mutation
  • Nuclear Proteins* / analysis
  • Nuclear Proteins* / genetics
  • Prognosis
  • Transcription Factors* / analysis
  • Transcription Factors* / genetics

Substances

  • Biomarkers, Tumor
  • DNA Helicases
  • Nuclear Proteins
  • SMARCA4 protein, human
  • Transcription Factors