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Clinicopathological and Genomic Analysis of SMARCA4-Deficient Non-Small Cell Lung Cancer: A Retrospective Cohort

Dongmei Chen1, Heng Zhang1,2, Diming Wang1

  • 1Department of Oncology, Anhui Chest Hospital, Hefei, Anhui, 230022, People's Republic of China.

Cancer Management and Research
|February 25, 2026
PubMed
Abstract

Insights

SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is an aggressive cancer. Early diagnosis and multimodal treatment are crucial for improving survival in patients with this rare subtype.

Area of Science:

  • Oncology
  • Pulmonology
  • Genetics

Background:

  • SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is a rare and aggressive subtype.
  • Limited treatment options exist for this challenging cancer.
  • Understanding its features is key to improving patient outcomes.

Purpose of the Study:

  • To analyze the clinical, pathological, molecular, and prognostic features of SMARCA4-dNSCLC.
  • To identify determinants of survival in patients with this rare lung cancer subtype.
  • To enhance the recognition and management of SMARCA4-dNSCLC.

Main Methods:

  • Retrospective cohort study of 47 SMARCA4-dNSCLC patients.
  • Defined SMARCA4 deficiency by loss of BRG1 expression via immunohistochemistry.
  • Analyzed clinical, imaging, histopathology, molecular, treatment, and survival data.

Main Results:

  • The cohort comprised older male smokers with advanced disease and necrotic masses.
  • BRG1 loss, TTF-1 negativity, and high Ki-67 were common; EGFR mutations were rare.
  • Median OS was not reached in treated patients vs. 3 months in untreated; advanced stage and lack of treatment were adverse prognostic factors.

Conclusions:

  • SMARCA4-dNSCLC is a distinct entity with poor prognosis.
  • Timely diagnosis and multimodal treatment are essential for survival.
  • Further prospective studies are needed to optimize treatment strategies.
Keywords:
BRG1 lossSMARCA4-deficient lung cancerimmunohistochemistrymolecular profilingprognosistreatment outcome

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