Clinicopathological characteristics and prognosis of SMARCA4/BRG1-deficient non-small cell lung cancer

ZHANG Jing; WANG Linlin; HU Jie

doi:10.3969/j.issn.1007-8096.2025.12.011

Abstract：Objective To investigate the clinicopathological characteristics and prognosis of SMARCA4/BRG1-deficient non-small cell lung cancer(NSCLC).Methods A total of 96 pathologically confirmed BRG1-intact or BRG1-deficient advanced NSCLC cases were analyzed.Additionally,NSCLC data containing SMARCA4 mutational profiles,mRNA expression levels and corresponding survival data were retrieved from TCGA and MSKCC databases.Results The main mutation types of SMARCA4 gene included missense mutation(52%),nonsense mutation(23%),frameshift deletion(12%),frameshift insertion(3%),and splice site mutation(10%).BRG1-deficient NSCLC was predominantly found in male(68.8%)with a history of tobacco exposure(65.6%)and a poor prognosis(median OS of 12.0 months).The histopathological types were diverse,with poorly differentiated adenocarcinomas being the most prevalent.The tumors were often accompanied by significant necrosis,brisk mitotic figures,and obvious inflammatory cell infiltration in the stroma.Additionally,TTF-1 was negatively expressed in 76.1%of cases and the median proliferative index of Ki-67 was 70%.While SMARCA4 mutational status lacked prognostic significance(P>0.05),both low SMARCA4 mRNA expression(P=0.03)and BRG1 protein deficiency(P<0.001)predicted a worse clinical prognosis.Conclusions SMARCA4/BRG1-deficient NSCLC exhibits highly aggressive clinicopathological phenotypes.The loss of BRG1 protein serves as a superior prognostic stratification factor compared to SMARCA4 gene alterations.