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SMARCA4 alterations in non-small cell lung cancer: a systematic review and meta-analysis
  1. Durgesh Wankhede1,2,
  2. Sandeep Grover3,
  3. Paul Hofman4,5,6
  1. 1 German Cancer Research Center, Heidelberg, Germany
  2. 2 Faculty of Medicine, Univeristy of Heidelberg, Heidelberg, Germany
  3. 3 Center for Human Genetics, Universitatsklinikum Giessen und Marburg - Standort Marburg, Marburg, Germany
  4. 4 Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, University Côte d'Azur, Nice, France
  5. 5 Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France
  6. 6 University Hospital Federation OncoAge, CHU de Nice, University Côte d'Azur, Nice, France
  1. Correspondence to Dr Durgesh Wankhede, German Cancer Research Center, Heidelberg, Germany; durgesh.wankhede{at}


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.

  • Lung Neoplasms

Data availability statement

Data are available on reasonable request. The data generated and analysed during the current study are available from the corresponding author on reasonable request.

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Data availability statement

Data are available on reasonable request. The data generated and analysed during the current study are available from the corresponding author on reasonable request.

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  • Handling editor Vikram Deshpande.

  • Contributors DW: conceptualisation, methodology, software, data curation, writing-original draft preparation, guarantor; PH: data curation, writing-reviewing, editing, supervision; SG: methodology, writing-reviewing, editing, supervision.

  • Funding The authors would like to thank the FHU OncoAge, 'Ligue Départementale 06 de Lutte contre le Cancer' and 'Conseii Départemental des Alpes Maritimes' for supporting the fee related to the publication of this manuscript.

  • Disclaimer The funder had no role in the development of this manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.