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A systematic review followed PRISMA guidelines and searched PubMed/MEDLINE and grey literature for studies assessing HERV expression in pancreatic cancer. Data covered HERV families and genomic regions, assays, specimen types, immune associations, clinicopathologic links, and survival metrics.",{"@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/human-endogenous-retroviruses-as-immune-related-prognostic-biomarkers-in-pancreatic-cancer/353399/",{"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/human-endogenous-retroviruses-as-immune-related-prognostic-biomarkers-in-pancreatic-cancer/353399.png","ImageObject",300,407,{"name":92,"@type":93},"LangkahRina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-22",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 primary aim of the systematic review?","Question",{"text":112,"@type":113},"To evaluate whether human endogenous retroviruses (HERVs) could serve as immune-related prognostic biomarkers in pancreatic cancer and to synthesize evidence across heterogeneous reports.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which HERV families and genomic elements were investigated?",{"text":117,"@type":113},"Studies assessed HERV-H and HERV-K, and some did not specify the family; reported elements included env sequences, envelope proteins, LTR sequences, and LTR-derived proteins such as HHLA2.",{"name":119,"@type":110,"acceptedAnswer":120},"How did HERV expression relate to immune features and patient survival?",{"text":121,"@type":113},"Immune correlations were reported with markers including CD8+ T-cell infiltration, cytokines (IL-2, TNF-α, IFN-γ), PD-1/PD-L1, and anti-HERV antibodies; survival associations included both adverse and favorable hazard ratios, with HHLA2-derived LTR products showing the most consistent favorable correlations.","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},353399,1790546658,{"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},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Toma etal. BMC Cancer (2026) 26:1003 BMC Cancer  \n[https://doi.org/10.1186/s12885-026-16373-9](https://doi.org/10.1186/s12885-026-16373-9)  \nSYSTEMATIC REVIEW Open Access  \nHuman endogenous retroviruses as immune- related prognostic biomarkers in pancreatic cancer  \nPaula IulianaToma 1,2*, Laurentia Nicoleta Gales1,3*, Francois Ghiringhelli4,5,6,7, Anda Trandafir1,8, Raluca Ioana Budea7 and Silvia Mihaela Ilie4,5,6,8  \nAbstract  \nBackground Human endogenous retroviruses (HERVs) may modulate antitumor immunity and prognosis in pancreatic cancer (PC), but reported findings remain heterogeneous.  \nMethods A systematic review was conducted according to PRISMA guidelines. PubMed/MEDLINE and grey literature were searched for studies reporting HERV expression in PC. Extracted data included HERV family and genomic region, detection methods, biological specimens, immune correlations, clinicopathologic associations, and survival outcomes.  \nResults Eleven studies were included, reporting 1,085 PC cases among 9,241 cancer patients. HERV-H was evaluated in 6 studies, HERV-K in 3, and 2 studies did not specify family. Elements included env sequences (3 studies), envelope proteins (2), LTR sequences (6), and LTR-derived proteins (HHLA2 (5) . Detection methods comprised RNA-seq (n = 7 studies), PCR/qPCR (n = 7), immunohistochemistry (n = 6), western blot (n = 4), and ELISA (n = 4) . HERV detection ranged from 16. 7% to ~ 80%, varying with the sequence and laboratory method. Immune correlations were described in 7 studies, including associations with CD8⁺ T-cell infiltration, cytokines (IL-2, TNF-α, IFN-γ), PD-1/PD-L1, and antiHERV antibodies. Overall survival was reported in 6 studies, with both adverse (HR 1.26–2. 24) and favourable (HR 0.47–0. 66) associations reported, particularly for HERV-H derived LTR products (HHLA2) .  \nConclusions HERVs exhibit frequent, target-dependent expression patterns that trigger proinflammatory activation. Within these families, HERV-H derived LTR elements, specifically HHLA2, demonstrate the most consistent correlation with increased T-cell infiltration and favorable survival, supporting their potential as prognostic biomarkers. Keywords Human endogenous retroviruses, Pancreatic ductal adenocarcinoma, Viral mimicry, Prognostic biomarkers, Systematic review  \n*Correspondence:  \nPaula IulianaToma [paula-iuliana. mazare@drd.umfcd. ro](paula-iuliana. mazare@drd.umfcd. ro)[ ](paula-iuliana. mazare@drd.umfcd. ro)Laurentia Nicoleta Gales [laurentia.gales@umfcd. ro](laurentia.gales@umfcd. ro)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.)  \nToma et al. BMC Cancer (2026) 26:1003 Page 2 of 15  \nGraphical abstract  \nIntroduction  \nHuman endogenous retroviruses (HERVs) and HERVlike sequences represent 8% of the human genome and are transmitted in a Mendelian manner [1, 2]. Although long considered as non-functional deoxyribonucleic acid (DNA) [3], they are now recognised as contributors to genome regulation and innate immune signalling [4]. ","cbCaihJQQRYQ2xq9","https://ap.wps.com/l/cbCaihJQQRYQ2xq9","pdf",1628636,15,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What was the primary aim of the systematic review?\",\"answer\":\"To evaluate whether human endogenous retroviruses (HERVs) could serve as immune-related prognostic biomarkers in pancreatic cancer and to synthesize evidence across heterogeneous reports.\"},{\"question\":\"Which HERV families and genomic elements were investigated?\",\"answer\":\"Studies assessed HERV-H and HERV-K, and some did not specify the family; reported elements included env sequences, envelope proteins, LTR sequences, and LTR-derived proteins such as HHLA2.\"},{\"question\":\"How did HERV expression relate to immune features and patient survival?\",\"answer\":\"Immune correlations were reported with markers including CD8+ T-cell infiltration, cytokines (IL-2, TNF-α, IFN-γ), PD-1/PD-L1, and anti-HERV antibodies; survival associations included both adverse and favorable hazard ratios, with HHLA2-derived LTR products showing the most consistent favorable correlations.\"}]","Human endogenous retroviruses as immune-related prognostic biomarkers in pancreatic cancer | PDF",1790105120,38]