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This retrospective study evaluated clinical, pathological, molecular, and prognostic characteristics to improve recognition and identify survival determinants. Methods: Forty-seven patients with pathologically confirmed SMARCA4-dNSCLC were included from July 2022 to January 2024. SMARCA4 deficiency was defined by loss of BRG1 on immunohistochemistry. Overall survival was assessed using Kaplan-Meier and Cox regression. Results: Patients were mainly older male smokers with advanced disease and large necrotic masses. BRG1 loss was common with frequent TTF-1 negativity and high Ki-67. TP53, KRAS, and STK11 mutations predominated; EGFR was rare. Advanced TNM stage, distant metastasis, and lack of treatment predicted poorer outcomes. Conclusion: The entity shows distinct clinicopathologic features and poor survival, supporting timely multimodal management and further prospective optimization.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/clinicopathological-and-genomic-analysis-of-smarca4-deficient-non-small-cell-lung-cancer-a-retrospective-cohort-study/358721/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/clinicopathological-and-genomic-analysis-of-smarca4-deficient-non-small-cell-lung-cancer-a-retrospective-cohort-study/358721.png","ImageObject",300,407,{"name":92,"@type":93},"Ezra","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"How was SMARCA4 deficiency defined in this study?","Question",{"text":111,"@type":112},"SMARCA4 deficiency was defined as loss of BRG1 expression by immunohistochemistry.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"What were the most common genetic alterations reported?",{"text":116,"@type":112},"Common alterations included TP53, KRAS, and STK11 mutations, while EGFR mutations were rare.",{"name":118,"@type":109,"acceptedAnswer":119},"Which factors were independent adverse prognostic indicators?",{"text":120,"@type":112},"Advanced TNM stage, distant metastasis, and absence of treatment were independent adverse prognostic factors (p\u003C0.05).","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},358721,1790194161,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},1099514068035,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Cancer Management and Research  \nOpen Access Full Text Article ORIGINAL RESEARCH  \nClinicopathological and Genomic Analysis of SMARCA4-Deficient Non-Small Cell Lung Cancer:  \nA Retrospective Cohort Study  \nDongmei Chen 1 , *, Heng Zhang 1 , 2 , *, Diming Wang 1 , Wei Ye 1 , 3 , Hongfei Zhao 1 , Chi Zhang 1 , Sihan Wu 1 , Qingming Shi 1  \n1Department of Oncology, Anhui Chest Hospital, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Thoracic Surgery II, Anhui Chest Hospital, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Pathology, Anhui Chest Hospital, Hefei, Anhui, 230022, People’s Republic of China  \n*These authors contributed equally to this work  \nCorrespondence: Qingming Shi, Email [shqm0324@163.com](shqm0324@163.com)  \n\n| Background: SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is a rare, aggressive subtype with limited treatment options. This study analyzed clinical, pathological, molecular, and prognostic features to improve recognition and identify survival determinants.\u003Cbr>Methods: This retrospective cohort study included 47 patients with pathologically confirmed SMARCA4-dNSCLC diagnosed at Anhui Chest Hospital between July 2022 and January 2024. SMARCA4 deficiency was defined as loss of BRG1 expression by immunohistochemistry. Clinical data, imaging findings, histopathology, molecular profiles, treatment modalities, and follow-up outcomes were reviewed. Overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards regression models to determine independent prognostic factors.\u003Cbr>Results: The cohort was predominantly older male smokers (median age 66; 87% male) with advanced disease (47% with distant metastasis at diagnosis) . Imaging typically showed large, necrotic masses with ill-defined borders. Adenocarcinoma was the most common subtype (60%) . Immunohistochemistry revealed BRG1 loss (91%), frequent TTF-1 negativity, and high Ki-67 expression. Common genetic alterations included TP53, KRAS, and STK11 mutations, while EGFR mutations were rare. Median overall survival was not reached in the treated group (median follow-up: 12.3 months; IQR: 8.5–15.1 months), compared with 3 months in the untreated group (median follow-up: 4.2 months; IQR: 2.8–5.6 months) . Advanced TNM stage, distant metastasis, and absence of treatment were independent adverse prognostic factors (p\u003C0.05) .\u003Cbr>Conclusion: SMARCA4-dNSCLC represents a distinct clinicopathologic entity with poor outcomes. Given the aggressive nature and poor prognosis of untreated SMARCA4-dNSCLC, timely diagnosis and multimodal treatment are essential to improving survival. Further prospective studies are needed to optimize management strategies.\u003Cbr>Keywords: SMARCA4-deficient lung cancer, BRG1 loss, immunohistochemistry, prognosis, treatment outcome, molecular profiling |\n| --- |\n| Introduction\u003Cbr>SMARCA4-dNSCLC is an emerging, biologically distinct, and highly aggressive subtype of lung cancer characterized by the inactivation of the SMARCA4 gene, 1–3 which encodes the BRG1 protein, a core catalytic subunit of the SWI/SNF chromatin remodeling complex.4–6 This subtype is increasingly recognized for its unique clinical and pathological features, most notably its predilection for older male patients with a history of heavy smoking.7\u003Cbr>The loss of BRG1 protein expression, as determined by immunohistochemistry, is a hallmark diagnostic feature of SMARCA4-dNSCLC.8,9 Histologically, these tumors frequently display poorly differentiated or undifferentiated morphology, often with rhabdoid or solid features, making diagnosis challenging, especially in small biopsy specimens.10–12 Moreover, these tumors typically lack common targetable driver mutations such as EGFR and ALK, limiting therapeutic options. As a result, conventional treatments including surgery, chemotherapy, and radiotherapy have shown limited efficacy in this population. Clinical outcomes remain dismal, with reported median OS as sh","cbCainvYMG5FxaL5","https://ap.wps.com/l/cbCainvYMG5FxaL5","pdf",2670908,13,"English","# Background\n# Methods\n# Results\n# Conclusion\n# Introduction","[{\"question\":\"How was SMARCA4 deficiency defined in this study?\",\"answer\":\"SMARCA4 deficiency was defined as loss of BRG1 expression by immunohistochemistry.\"},{\"question\":\"What were the most common genetic alterations reported?\",\"answer\":\"Common alterations included TP53, KRAS, and STK11 mutations, while EGFR mutations were rare.\"},{\"question\":\"Which factors were independent adverse prognostic indicators?\",\"answer\":\"Advanced TNM stage, distant metastasis, and absence of treatment were independent adverse prognostic factors (p\\u003c0.05).\"}]","Clinicopathological and Genomic Analysis of SMARCA4-Deficient Non-Small Cell Lung Cancer - A Retrospective Cohort Study | PDF",1790135069,33]