Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer

Cancer Med. 2023 Jul;12(13):14171-14182. doi: 10.1002/cam4.6083. Epub 2023 May 15.

Abstract

Purpose: To improve the understanding of special types of tumors, we summarized and analyzed the clinicopathological features and prognostic factors of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC).

Methods: We selected 105 patients with SMARCA4-dNSCLC and 221 patients with SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) by performing immunohistochemical analysis of 1520 NSCLC samples, and we assessed the patients' clinicopathological features and survival state.

Results: (1) SMARCA4-dNSCLC was significantly associated with older age, male sex, smoking history, larger invasive tumor size, higher tumor proliferation index (Ki-67), more adrenal metastases, more lymph node metastases, and few EGFR mutations (p < 0.05). The tumors were mostly negative for thyroid transcription factor-1 (TTF-1), CD34, and p40 and positive for cytokeratin 7 (CK7) in immunohistochemistry (IHC). Nineteen SMARCA4-dNSCLC patients mostly had TP53, SMARCA4, and LRP1B mutations, and 48% of them had SMARCA4 frameshift mutations. SMARCA4-dNSCLC patients have a worse prognosis than SMARCA4-iNSCLC patients (HR: 0.27; 95% CI: 0.17-0.45). The overall survival (OS) of patients with stage III SMARCA4-dNSCLC was worse than that of patients with SMARCA4-iNSCLC, and the OS of stage IV SMARCA4-dNSCLC patients was also worse than that of SMARCA4-iNSCLC patients (p < 0.01). (2) Multivariate regression analysis showed that sex (HR: 4.12; 95% CI: 1.03-16.39) and smoking history (HR: 2.29; 95% CI: 1.04-5.02) had significant effects on the survival time of SMARCA4-dNSCLC patients. In SMARCA4-dNSCLC patients without distant metastases (stage I-III), patients with stage N2 or N3 lymph node metastases (HR: 6.35; 95% CI: 1.07-37.47) had a poor prognosis. Among patients with SMARCA4-dNSCLC who were treated and had distant metastases (stage IV), male patients and patients treated with immunotherapy combined with chemotherapy showed a longer median overall survival (mOS).

Conclusion: SMARCA4-dNSCLC has unique clinicopathological features and a shorter survival prognosis than SMARCA4-iNSCLC. The efficacy of immunotherapy combined with chemotherapy needs to be observed for longer periods.

Keywords: BRG1; EGFR mutation; SMARCA4; lung cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung* / diagnosis
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • DNA Helicases / genetics
  • Humans
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / therapy
  • Lymphatic Metastasis
  • Male
  • Nuclear Proteins / genetics
  • Prognosis
  • Transcription Factors / metabolism

Substances

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