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Pan-cancer HIC1 expression and tumor–normal differential patterns are analyzed, with validation by immunohistochemistry in clinical cohorts. Prognostic value is assessed using Kaplan–Meier and Cox models, followed by genetic alteration, GSEA pathway analysis, and correlation with TMB, MSI, and PD-1/PD-L1 inhibitor efficacy, plus drug sensitivity profiling from public databases.",{"@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/ferroptosis-related-gene-hic1-in-the-prediction-of-the-prognosis-and-immunotherapeutic-efficacy-with-immunological-activity/376960/",{"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/ferroptosis-related-gene-hic1-in-the-prediction-of-the-prognosis-and-immunotherapeutic-efficacy-with-immunological-activity/376960.png","ImageObject",300,407,{"name":92,"@type":93},"Connor ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",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},"What was the study aimed to clarify about HIC1?","Question",{"text":112,"@type":113},"The study aimed to determine how the ferroptosis-related gene HIC1 relates to pan-cancer prognosis and immunotherapeutic efficacy, and to assess its connections with immune activity in the tumor immune microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was HIC1 expression evaluated and validated?",{"text":117,"@type":113},"HIC1 expression across pan-cancer and differential expression between tumor and normal samples were analyzed, and immunohistochemistry (IHC) was used to validate HIC1 expression in clinical cohorts including lung cancer, sarcoma, breast cancer, and kidney renal clear cell carcinoma.",{"name":119,"@type":110,"acceptedAnswer":120},"Which biomarkers and treatment responses were linked to HIC1?",{"text":121,"@type":113},"HIC1 correlated with immune cell infiltration and immune-related pathways, showed relationships with TMB and MSI, and was significantly associated with response to PD-1/PD-L1 inhibitors, as well as sensitivity to multiple anti-cancer drugs.","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},376960,1790480392,{"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":145},687207022233,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","TYPE Original Research PUBLISHED 14 June 2023  \nDOI 10.3389/fimmu.2023.1182030  \nOPEN ACCESS  \nEDITED BYEsra Akbay,  \nUniversity of Texas Southwestern Medical Center, United States  \nREVIEWED BY Rui Sha,  \nFirst Affiliated Hospital of Wannan Medical College, China  \nSubhayan Das,  \nIndian Institute of Technology Kharagpur, India  \n*CORRESPONDENCE Tang Liu  \n [liutang1204@csu.edu.cn](liutang1204@csu.edu.cn)[ ](liutang1204@csu.edu.cn)Zhihong Li  \n [lizhihong@csu.edu.cn](lizhihong@csu.edu.cn)  \n†These authors have contributed equally to this work and share first authorship  \nRECEIVED 08 March 2023  \nACCEPTED 31 May 2023  \nPUBLISHED 14 June 2023  \nCITATION  \nWu Y, Lin Z, Tang X, Tong Z, Ji Y, Xu Y, Zhou Z, Yang J, Li Z and Liu T (2023) Ferroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity.  \nFront. Immunol. 14:1182030 .  \ndoi: 10.3389/fimmu.2023.1182030  \nCOPYRIGHT  \n© 2023 Wu, Lin, Tang, Tong, Ji, Xu, Zhou, Yang, Li and Liu. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nFerroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity  \nYanlin Wu 1†, Zhengjun Lin 1†, Xianzhe Tang2, Zhongyi Tong 3, Yuqiao Ji 1, Yingting Xu 1, Ziting Zhou 1, Jing Yang 1, Zhihong Li 1* and Tang Liu 1*  \n1 Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China, 2 Department of Orthopedics, Chenzhou No. 1 People’s Hospital, Chenzhou, Hunan, China, 3 Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China  \nBackground: Hypermethylated in Cancer 1 (HIC1) was originally confirmed as a tumor suppressor and has been found to be hypermethylated in human cancers. Although growing evidence has supported the critical roles of HIC1 in cancer initiation and development, its roles in tumor immune microenvironment and immunotherapy are still unclear, and no comprehensive pan-cancer analysis of HIC1 has been conducted.  \nMethods: HIC1 expression in pan-cancer, and differential HIC1 expression between tumor and normal samples were investigated. Immunohistochemistry (IHC) was employed to validate HIC1 expression in different cancers by our clinical cohorts, including lung cancer, sarcoma (SARC), breast cancer, and kidney renal clear cell carcinoma (KIRC) . The prognostic value of HIC1 was illustrated by Kaplan-Meier curves and univariate Cox analysis, followed by the genetic alteration analysis of HIC1 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was conducted to illustrate the signaling pathways and biological functions of HIC1 . The correlations between HIC1 and tumor mutation burden (TMB), microsatellite instability (MSI), and the immunotherapy efficacy of PD-1/ PD-L1 inhibitors were analyzed by Spearman correlation analysis. Drug sensitivity analysis of HIC1 was performed by extracting data from the CellMiner™ database.  \nResults: HIC1 expression was abnormally expressed in most cancers, and remarkable associations between HIC1 expression and prognostic outcomes of patients in pan-cancer were detected. HIC1 was significantly correlated with T cells, macrophages, and mast cell infiltration in different cancers. Moreover, GSEA revealed that HIC1 was significantly involved in immune-related biological functions and signaling pathways. There was a close relationship of HIC1 with TMB and MSI in different cancers. Furthermore, the most exciting finding was that HIC1 expression was significantly correlated with the response to PD-1/PD-L1 inhibitors in ca","cbCainuKTe0tWEfq","https://ap.wps.com/l/cbCainuKTe0tWEfq","pdf",23391766,18,"English","# Background\n# Methods\n# Results\n# Conclusions\n# Keywords","[{\"question\":\"What was the study aimed to clarify about HIC1?\",\"answer\":\"The study aimed to determine how the ferroptosis-related gene HIC1 relates to pan-cancer prognosis and immunotherapeutic efficacy, and to assess its connections with immune activity in the tumor immune microenvironment.\"},{\"question\":\"How was HIC1 expression evaluated and validated?\",\"answer\":\"HIC1 expression across pan-cancer and differential expression between tumor and normal samples were analyzed, and immunohistochemistry (IHC) was used to validate HIC1 expression in clinical cohorts including lung cancer, sarcoma, breast cancer, and kidney renal clear cell carcinoma.\"},{\"question\":\"Which biomarkers and treatment responses were linked to HIC1?\",\"answer\":\"HIC1 correlated with immune cell infiltration and immune-related pathways, showed relationships with TMB and MSI, and was significantly associated with response to PD-1/PD-L1 inhibitors, as well as sensitivity to multiple anti-cancer drugs.\"}]","Ferroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity | PDF",1790222387,45]