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

Abstract

The objective of the study is to investigate the clinicopathological features and prognostic factors of SMARCA4-deficient non-small cell lung cancer (SMARCA4-deficient NSCLC). A total of 43 patients with SMARCA4-deficient NSCLC who were diagnosed at Baotou Steel Hospital between January 2021 and October 2024 were included. Kaplan-Meier survival curves were plotted, and the log-rank test was used for group comparisons. Cox regression analysis was performed to identify factors influencing the 2-year overall survival in SMARCA4-deficient NSCLC patients. SMARCA4-deficient NSCLC patients exhibited distinct characteristics: older age (P < 0.05), male predominance (P < 0.05), smoking history (P < 0.05), larger tumors (P < 0.05), higher Ki-67 index (P < 0.05), lower EGFR mutation rates (P < 0.05), fewer squamous carcinomas (P < 0.05), and more poorly differentiated tumors (P < 0.05). Immunohistochemistry revealed BRG1 loss in 93.0 % (40/43), with TTF-1 (76.7 %) and P40 (81.4 %) negativity. The 2-year survival rate was significantly worse in SMARCA4-deficient NSCLC vs. SMARCA4-intact NSCLC (log-rank P < 0.001). Multivariate Cox analysis identified age ≥ 65 years (HR = 2.8, P = 0.003), smoking (HR = 2.4, P = 0.012), tumor size >5 cm (HR = 3.1, P < 0.001), and distant metastasis (HR = 4.5, P < 0.001) as independent predictors of poor survival in SMARCA4-deficient NSCLC. Patients with advanced-stage disease (III/IV) had significantly shorter survival (P < 0.05). SMARCA4 deficiency defines an aggressive NSCLC subtype with unique clinicopathological traits, including rapid progression, and poor survival.