中国肺癌杂志2026，Vol.29Issue(3)：180-189,10.DOI:10.3779/j.issn.1009-3419.2026.106.09
18例SMARCA4缺失或基因突变肺部肿瘤患者的临床病理与基因特征以及预后分析
Clinicopathological,Genomic Characteristics and Prognostic Analysis in 18 Cases of SMARCA4-deficient or SMARCA4-mutated Pulmonary Tumors
摘要
Abstract
Background and objective The diagnosis of SMARCA4-altered pulmonary tumors primarily relies on the detection of protein loss by immunohistochemistry(IHC).However,the concordance between IHC and genetic testing re-sults,as well as the clinical and biological differences caused by various mutation types,require further investigation.This study aimed to explore the clinicopathological,genomic characteristics,as well as the prognosis,of these tumors.Methods A total of 18 consecutive cases of pulmonary tumor patients with SMARCA4 deficiency/mutation confirmed by IHC or genetic testing were retrospectively enrolled for clinical,genomic,and prognostic analysis.Based on the variant type,patients were categorized into Class 1(protein loss or loss-of-function gene mutations,n=10)and Class 2(missense mutation or other variants of un-known significance without protein loss,n=8)for intergroup comparison.Results Seventeen cases were diagnosed with non-small cell lung cancer(NSCLC)and one was diagnosed with thoracic SMARCA4-deficient undifferentiated tumor(SD-UT).Genotype-phenotype correlation analysis revealed that truncating mutations consistently led to protein loss,whereas missense mutations mostly did not.Two cases with protein loss but negative genetic testing results were identified.Class 1 alterations showed trends towards higher tumor mutational burden(TMB)(median 9.3 vs 4.7 Muts/Mb)and lower programmed cell death ligand 1(PD-L1)expression(60.0%vs 25.0%with<1%expression)compared to Class 2,but the differences were not statistically significant(P>0.05).Two patients with co-occurring epidermal growth factor receptor(EGFR)L858R mutations showed poor initial response to third-generation EGFR-tyrosine kinase inhibitor monotherapy,but the efficacy was observed after combination with other therapies.Among stage IV patients,the median overall survival(OS)was 10.3 months for Class 1 and 19.9 months for Class 2(P=0.967).Fourteen patients(77.8%)received immune checkpoint inhibitors(ICIs)combined with chemotherapy.Among them,8 patients(57.1%)achieved an OS exceeding 12 months,and 7 patients(50.0%)exceeded 24 months.Conclusion SMARCA4 gene mutations are not entirely consistent with IHC protein loss,necessitating combined interpretation.When SMARCA4 alterations co-exist with EGFR mutations,targeted monotherapy efficacy may be limited,and combination strategies should be considered.Classifying SMARCA4 alterations into Class 1 and Class 2 may have prognostic implications and could help predict the tumor immune microenvironment status(TMB and PD-L1).ICIs combined with che-motherapy is currently one of the main treatment options for patients with advanced SMARCA4-altered pulmonary tumors and showed potential efficacy in this study.关键词
肺肿瘤/胸部SMARCA4缺失型未分化肿瘤/SMARCA4突变/SMARCA4(BRG1)缺失/EGFR突变/靶向治疗/免疫检查点抑制剂/预后Key words
Lung neoplasms/Thoracic SMARCA4-deficient undifferentiated tumor/SMARCA4 mutation/SMARCA4(BRG1)deficiency/EGFR mutation/Targeted therapy/Immune checkpoint inhibitors/Prognosis引用本文复制引用
刘畅,杨晶,孟凡路,张琳琳,王鑫,于涛,钟殿胜..18例SMARCA4缺失或基因突变肺部肿瘤患者的临床病理与基因特征以及预后分析[J].中国肺癌杂志,2026,29(3):180-189,10.基金项目
本研究受国家自然科学基金项目(No.82272672)和天津医科大学总医院青年专业技术骨干基金项目(No.GG-2021-13)资助 This study was supported by the grants from National Natural Science Foundation of China(No.82272672,to Dian-sheng ZHONG)and Tianjin Medical University General Hospital Youth Professional and Technical Backbone Project(No.GG-2021-13,to Chang LIU). （No.82272672）
