[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-339333-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-339333-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","serum-itih5-as-a-novel-diagnostic-biomarker-in-cholangiocarcinoma","Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma","","Cholangiocarcinoma often remains undetected until advanced stages because reliable diagnostic markers are lacking. The study aimed to identify a unique secretory protein for diagnosis and differentiation from other malignancies, benign hepatobiliary diseases, and chronic liver conditions. Bulk RNA-seq, single-cell RNA sequencing, and protein validation by immunohistochemistry and ELISA showed ITIH5 was specifically upregulated and secreted, with serum levels distinguishing patients from controls.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/serum-itih5-as-a-novel-diagnostic-biomarker-in-cholangiocarcinoma/339333/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/serum-itih5-as-a-novel-diagnostic-biomarker-in-cholangiocarcinoma/339333.png","ImageObject",300,407,{"name":42,"@type":43},"Aurora","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is early diagnosis of cholangiocarcinoma difficult?","Question",{"text":63,"@type":64},"Early diagnosis is challenging due to its anatomical location, silent clinical presentation, and lack of clear diagnostic criteria, leading many patients to be diagnosed at advanced stages.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What is ITIH5 and how is it evaluated in this study?",{"text":68,"@type":64},"ITIH5 is an extracellular secretory protein encoded by a gene. The study evaluates its expression using bulk RNA-seq and single-cell RNA sequencing, then confirms tissue and serum levels with immunohistochemistry and ELISA.",{"name":70,"@type":61,"acceptedAnswer":71},"How well does serum ITIH5 distinguish cholangiocarcinoma from controls?",{"text":72,"@type":64},"Serum ITIH5 levels are elevated in cholangiocarcinoma, and ROC analysis shows AUC values between 0.839 and 0.851 for distinguishing patients from controls.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},339333,1790242719,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},4810365810221,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Received: 28 November 2023 | Revised: 5 February 2024 | Accepted: 25 February 2024  \nDOI: 10. 1111/cas.16143  \nOR I G I NAL ART I C L E  \nSerum ITIH5 as a novel diagnostic biomarker incholangiocarcinoma  \nMeiru Chen1,2 | Jinghan Ma3 | Xiaoli Xie1 | Miao Su2 | Dongqiang Zhao1   \n1Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei Province, China 2Department of Gastroenterology, Hengshui People's Hospital, Hengshui, Hebei Province, China  \n3 Department of Rheumatology and immunology, The Second Hospital of Hebei Medical University, Shijiazhuang,  \nHebei Province, China  \nCorrespondence  \nDongqiang Zhao, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei Province 050000, China.  \nEmail: [hbzdq1998@163.com](hbzdq1998@163.com)  \nFunding information  \nNatural Science Foundation of Hebei Province, Grant/Award Number:  \nH2022206539  \nAbstract  \nCholangiocarcinoma often remains undetected until advanced stages due to the lack of reliable diagnostic markers. Our goal was to identify a unique secretory protein for cholangiocarcinoma diagnosis and differentiation from other malignancies, benign hepatobiliary diseases, and chronic liver conditions. We conducted bulk RNA-seq analysis to identify genes specifically upregulated in cholangiocarcinoma but not inmost other cancers, benign hepatobiliary diseases, and chronic liver diseases focusing on exocrine protein-encoding genes. Single-cell RNA sequencing examined subcellular distribution. Immunohistochemistry and enzyme-linked immunosorbent assays assessed tissue and serum expression. Diagnostic performance was evaluated via receiver-operating characteristic (ROC) analysis. Inter-alpha-trypsin inhibitor heavy chain family member five (ITIH5), a gene encoding an extracellular protein, is notably upregulated in cholangiocarcinoma. This elevation is not observed in most other cancer types, benign hepatobiliary diseases, or chronic liver disorders. It is specifically expressed by malignant cholangiocytes. ITIH5 expression in cholangiocarcinoma tissues exceeded that in nontumorous bile duct, hepatocellular carcinoma, and nontumorous hepatic tissues. Serum ITIH5 levels were elevated in cholangiocarcinoma compared with controls (hepatocellular carcinoma, benign diseases, chronic hepatitis B, and healthy individuals) . ITIH5 yielded areas under the ROC curve (AUCs) from 0.839 to 0.851 distinguishing cholangiocarcinoma from controls. Combining ITIH5 with carbohydrate antigen 19-9 (CA19-9) enhanced CA19-9's diagnostic effectiveness. In conclusion, serum ITIH5 may serve as a novel noninvasive cholangiocarcinoma diagnostic marker.  \nK E Y WO R D S  \ncholangiocarcinoma, diagnosis, ELISA, ITIH5, serum marker  \nAbbreviations: AUC, the area under the receiver-operating characteristic curve; CA19-9, carbohydrate antigen 19-9; CCA, cholangiocarcinoma; dCCA, distal cholangiocarcinoma; DEGs, differential expression genes; ELISA, enzyme-linked immunosorbent assay; EP-upDEGs, exocrine protein-upregulated differentially expressed genes; GEO, Gene Expression Omnibus; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma; IHC, immunohistochemistry; ITIH5, inter-alpha-trypsin inhibitor heavy chain family member five; NASH, nonalcoholic steatohepatitis; NCCA, the total patients without CCA; PCA, principal components analysis; pCCA, perihilar cholangiocarcinoma; PSC, primary sclerosing cholangitis; ROC, receiver-operating characteristic; scRNA-seq, single-cell RNA sequencing; TCGA, The Cancer Genome Atlas; UMAP, Uniform Manifold Approximation and Projection.  \nThis is an open access article under the terms of the Creative Commons Attribution-","cbCaibz2jmf6Y6Ju","https://ap.wps.com/l/cbCaibz2jmf6Y6Ju","pdf",4094312,15,"English","# Abstract\n# Introduction","[{\"question\":\"Why is early diagnosis of cholangiocarcinoma difficult?\",\"answer\":\"Early diagnosis is challenging due to its anatomical location, silent clinical presentation, and lack of clear diagnostic criteria, leading many patients to be diagnosed at advanced stages.\"},{\"question\":\"What is ITIH5 and how is it evaluated in this study?\",\"answer\":\"ITIH5 is an extracellular secretory protein encoded by a gene. The study evaluates its expression using bulk RNA-seq and single-cell RNA sequencing, then confirms tissue and serum levels with immunohistochemistry and ELISA.\"},{\"question\":\"How well does serum ITIH5 distinguish cholangiocarcinoma from controls?\",\"answer\":\"Serum ITIH5 levels are elevated in cholangiocarcinoma, and ROC analysis shows AUC values between 0.839 and 0.851 for distinguishing patients from controls.\"}]","Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma | PDF",1790029660,38]