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Immune microenvironments in these sites have not been comprehensively profiled. RNA from FFPE sections of 34 tumors and matched non-SRCC controls was analyzed using a PanCancer immune profiling panel of 770 immune genes. Colorectal and gastric SRCC showed distinct immune gene expression profiles versus non-SRCC adenocarcinomas.",{"@graph":69,"@context":122},[70,84,105],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/comprehensive-characterization-of-the-immune-microenvironment-of-colorectal-and-gastric-signet-ring-cell-cancer/465385/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/comprehensive-characterization-of-the-immune-microenvironment-of-colorectal-and-gastric-signet-ring-cell-cancer/465385.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is signet ring cell carcinoma considered clinically aggressive?","Question",{"text":112,"@type":113},"SRCC is linked to a more aggressive phenotype than non-signet ring adenocarcinoma in the same organ, including poorer prognosis independent of stage and distinctive clinical behavior.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the immune microenvironment characterized in the study?",{"text":117,"@type":113},"RNA was isolated from FFPE tumor sections, and expression was assessed using a PanCancer Immune Profiling Panel covering 770 immune-related genes.",{"name":119,"@type":110,"acceptedAnswer":120},"What immune differences were observed between SRCC and non-SRCC?",{"text":121,"@type":113},"Colorectal and gastric SRCC showed distinct immune-related gene expression profiles compared with non-SRCC, including enrichment of pathways associated with innate immune response and complement activity.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},465385,1790832271,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Article  \nComprehensive Characterization of the Immune Microenvironment of Colorectal and Gastric Signet Ring Cell Cancer  \nJianqing Zhang 1, Robin Collingwood 2, Sameer Al Diffalha 3, Deborah Della Manna 1, Ravi Kumar Paluri 4, Haider A. Mejbel 5 and Olumide Gbolahan 6, *  \nAcademic Editors: Federica Laudisi and Carmine Stolfi  \nReceived: 16 October 2025  \nRevised: 9 December 2025  \nAccepted: 12 December 2025  \nPublished: 23 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [jianqingzhang@uabmc.edu](jianqingzhang@uabmc.edu) (J.Z.)  \n2 Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA 19104, USA  \n3 Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA  \n4 Department of Hematology and Medical Oncology, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA  \n5 Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA; [haider.a.mejbel@emory.edu](haider.a.mejbel@emory.edu)  \n6 Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA 30322, USA  \n* Correspondence: [ogbolah@emory.edu](ogbolah@emory.edu); Tel.: +1-404-778-1670  \nHighlights  \nWhat are the main findings?  \n• The immune components of gastric and colorectal SRCCs are distinct from their corresponding non-SRCC counterparts.  \n• IL13RA2 was identified as a potential biomarker and therapeutic target candidate for colorectal SRCC.  \nWhat are the implications of the main findings?  \n• Gastric and colorectal SRCC tumors likely employ immune evasion mechanisms.  \n• Overall, our descriptive study highlights pathways (IL-13, complement) that may be targeted for drug development in SRCC.  \nAbstract  \nThe reasons for the aggressive clinical phenotype of signet ring cell carcinoma (SRCC) have not been fully elucidated. Previous studies suggest similarities in the genotype of colorectal and gastric SRCC and a clear distinction from non-SRCC. The immune microenvironments of gastric and colorectal SRCC have not been comprehensively examined. We isolated RNA from formalin-fixed, paraffin-embedded (FFPE) sections of 34 tumor specimens, 10 colorectal SRCC, 24 gastric SRCC, 4 non-SRCC colorectal (CCC), and 3 gastric adenocarcinoma (GCC) samples. The PanCancer Immune Profiling Panel was used to evaluate the expression of 770 immune-related genes. We compared the expression profiles of colorectal and gastric SRCC and non-SRCC adenocarcinoma. We found that the immune-related gene expression profiles (GEPs) of colorectal SRCC (CR-SRCC) and gastric SRCC (G-SRCC) were distinct from the non-SRCC. A total of 127 genes were upregulated and 32 downregulated in CR-SRCC compared to CCC. Only two genes (CCL27 and LAIR2 reached statistical significance (p-adj \u003C 0.05)) among the differentially expressed genes in G-SRCC compared to GCC. None of the clinically relevant immune checkpoints were significantly differentially expressed in SRCC vs. non-SRCC. Overall, we noted a relative abundance of CD8+ cells in  \nCR-SRCC and G-SRCC and relative overexpression of genes involved in innate immune response including the complement pathway. Finally, we identified IL13RA2 as a potential biomarker and therapeutic target candidate for CR-SRCC. The immune microenvironments of CR-SRCC and G-SRCC are distinct from non-SRCC. Broadly, both CR-SRCC and G-SRCCare characterized by a complex immune microenvironment that features cytotoxic cells and innate immune activity that may facilitate immune evasion.  \nKeywords: signet ring cell cancer; colorectal cancer; ga","cbCailsUyD1OsHg0","https://ap.wps.com/l/cbCailsUyD1OsHg0","pdf",2662282,16,"English","# Highlights\n## Main findings\n## Implications\n# Abstract\n# Keywords\n# Introduction","[{\"question\":\"Why is signet ring cell carcinoma considered clinically aggressive?\",\"answer\":\"SRCC is linked to a more aggressive phenotype than non-signet ring adenocarcinoma in the same organ, including poorer prognosis independent of stage and distinctive clinical behavior.\"},{\"question\":\"How was the immune microenvironment characterized in the study?\",\"answer\":\"RNA was isolated from FFPE tumor sections, and expression was assessed using a PanCancer Immune Profiling Panel covering 770 immune-related genes.\"},{\"question\":\"What immune differences were observed between SRCC and non-SRCC?\",\"answer\":\"Colorectal and gastric SRCC showed distinct immune-related gene expression profiles compared with non-SRCC, including enrichment of pathways associated with innate immune response and complement activity.\"}]","Comprehensive Characterization of the Immune Microenvironment of Colorectal and Gastric Signet Ring Cell Cancer | PDF",1790769561]