摘要
目的探讨SMARCA4/BRG1缺失型非小细胞肺癌(NSCLC)的临床病理特征及预后。方法选取96例经病理确诊的BRG1表达或缺失的晚期NSCLC病例,下载TCGA及MSKCC数据库中含有SMARCA4基因突变谱、mRNA表达水平及相应预后信息的NSCLC数据。结果SMARCA4基因的主要突变类型包括错义突变(52%),无义突变(23%),移码缺失(12%),移码插入(3%),以及剪切位点突变(10%)。BRG1缺失型NSCLC主要以男性为主(占比68.8%),65.6%有烟草暴露史,中位生存期仅12.0个月。病理组织学类型多样,以低分化腺癌多见,肿瘤常伴显著坏死,核分裂象易见,间质有显著的炎细胞浸润,76.1%的病例呈TTF-1阴性表达,Ki-67的中位表达水平为70%。SMARCA4突变与否对总生存率无预测价值(P>0.05),而SMARCA4mRNA低表达(P=0.03)及BRG1蛋白缺失(P<0.001),提示更差的临床预后。结论SMARCA4BRG1缺失型NSCLC具有高度侵袭性的临床病理表型,BRG1蛋白缺失较SMARCA4基因突变能更好地作为患者预后分层的评估指标。
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.
作者
张静
王林林
胡洁
ZHANG Jing;WANG Linlin;HU Jie(Department of Respiratory and Critical Care Medicine,Shanghai Geriatric Center/Zhongshan Hospital Minhang Division,Fudan University,Shanghai 201104,China;Department of Respiratory and Critical Care Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China)
出处
《诊断病理学杂志》
2025年第12期1592-1598,共7页
Chinese Journal of Diagnostic Pathology
