{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T20:13:49Z","timestamp":1771964029781,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009873","name":"Regione Autonoma della Sardegna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Emerging evidence has proven that human endogenous retroviruses (HERVs) play a critical role in the pathogenesis of Acute Myeloid Leukemia (AML), whereas the specific HERVs influencing the prognosis of AML patients have yet to be fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, a systematic exploration was achieved to identify potential prognostic HERVs for AML, sourced from TCGA and GTEx database. Differential analysis and functional enrichment studies were conducted using GO, KEGG, GSEA, and GSVA. The ESTIMATE algorithm was applied to explore the immune infiltration of HERVs in AML. A prognostic risk-score model was evaluated with predicted yearly accuracy using ROC analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two HERVs Suppressyn and Syncytin-2, were identified as promising prognostic biomarkers, with high discrimination ability based on ROC analysis between AML and healthy cohorts from TCGA. Their expression was notably higher in AML patients compared to those in healthy individuals but correlates with favorable clinical outcomes in sub-groups such as white race, lower WBC counts, favorable and intermediate risks, and NPM1 or IDH1 mutation. Suppressyn and Syncytin-2 participated in immune-related pathways and exhibited correlations with multiple immune infiltration cells, such as T cells, mast cells, and tumor-associated macrophages. Finally, we developed a prognostic risk-scoring model combining Suppressyn and Syncytin-2, where a high risk-score is associated with better prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Collectively, our findings revealed that Suppressyn and Syncytin-2 may act as valuable diagnostic and prognostic biomarkers for individuals with AML, while highlighting links between HERV activation, immunogenicity, and future therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1339673","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T04:39:31Z","timestamp":1704947971000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Endogenous retroviruses Suppressyn and Syncytin-2 as innovative prognostic biomarkers in Acute Myeloid Leukemia"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiaxin","family":"Shen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofen","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyang","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Fozza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo Antonio","family":"Sechi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1182\/bloodadvances.2021005789","article-title":"Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation","volume":"7","author":"Bill","year":"2023","journal-title":"Blood Adv."},{"key":"B2","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.immuni.2013.10.003","article-title":"Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer","volume":"39","author":"Bindea","year":"2013","journal-title":"Immunity"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1752-0509-8-s4-s11","article-title":"cytoHubba: identifying hub objects and sub-networks from complex interactome","author":"Chin","year":"2014","journal-title":"BMC Syst. Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3506","DOI":"10.1038\/s41467-020-17206-4","article-title":"Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia","volume":"11","author":"Deniz","year":"2020","journal-title":"Nat. Commun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/apm.12474","article-title":"Expression and function of endogenous retroviruses in the placenta","volume":"124","author":"Denner","year":"2016","journal-title":"Apmis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"D\u00f6hner","year":"2017","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1002\/ajh.25517","article-title":"The combination of NPM1, DNMT3A, and IDH1\/2 mutations leads to inferior overall survival in AML","volume":"94","author":"Dunlap","year":"2019","journal-title":"Am. J. Hematol."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.637981","article-title":"Identification of differentially expressed human endogenous retrovirus families in human leukemia and lymphoma cell lines and stem cells","volume":"11","author":"Engel","year":"2021","journal-title":"Front. Oncol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-22-3140","article-title":"Elevated mast cell abundance is associated with enrichment of CCR2+ Cytotoxic T cells and favorable prognosis in lung adenocarcinoma","author":"Fan","year":"2023","journal-title":"Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1126\/science.abq7871","article-title":"Evolution and antiviral activity of a human protein of retroviral origin","volume":"378","author":"Frank","year":"2022","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00462","article-title":"HERV envelope proteins: physiological role and pathogenic potential in cancer and autoimmunity","volume":"9","author":"Grandi","year":"2018","journal-title":"Front. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/s41375-021-01432-w","article-title":"Acute myeloid leukemia cell membrane-coated nanoparticles for cancer vaccination immunotherapy","volume":"36","author":"Johnson","year":"2022","journal-title":"Leukemia"},{"key":"B13","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-immunol-101721-033341","article-title":"The immunological conundrum of endogenous retroelements","volume":"41","author":"Kassiotis","year":"2023","journal-title":"Annu. Rev. Immunol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422x-11-58","article-title":"Vaccination directed against the human endogenous retrovirus-K (HERV-K) gag protein slows HERV-K gag expressing cell growth in a murine model system","volume":"11","author":"Kraus","year":"2014","journal-title":"Virol. J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00740-7","article-title":"Widespread and tissue-specific expression of endogenous retroelements in human somatic tissues","volume":"12","author":"Larouche","year":"2020","journal-title":"Genome Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"12000","DOI":"10.1200\/JCO.2018.36.15_suppl.12000","article-title":"Association of high tissue TMB and atezolizumab efficacy across multiple tumor types","volume":"36","author":"Legrand","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/978-1-4614-7651-1_7","article-title":"Cellular entry of retroviruses","volume":"790","author":"Lindemann","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/v12080852","article-title":"Contribution of human retroviruses to disease development-A focus on the HIV- and HERV-cancer relationships and treatment strategies","volume":"12","author":"Liu","year":"2020","journal-title":"Viruses"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1093\/bioinformatics\/btt138","article-title":"Cytoscape app store","volume":"29","author":"Lotia","year":"2013","journal-title":"Bioinformatics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.semcancer.2018.10.001","article-title":"Human endogenous retroviruses role in cancer cell stemness","volume":"53","author":"Matteucci","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.145363","article-title":"Expression of ERV3-1 in leukocytes of acute myelogenous leukemia patients","volume":"773","author":"Nakagawa","year":"2021","journal-title":"Gene"},{"key":"B23","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41586-023-05771-9","article-title":"Antibodies against endogenous retroviruses promote lung cancer immunotherapy","volume":"616","author":"Ng","year":"2023","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic classification and prognosis in acute myeloid leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N Engl. J. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"503","DOI":"10.6004\/jnccn.2023.0025","article-title":"Acute myeloid leukemia, version 3.2023, NCCN clinical practice guidelines in oncology","volume":"21","author":"Pollyea","year":"2023","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12020162","article-title":"Endogenous retroviruses as modulators of innate immunity","volume":"12","author":"Russ","year":"2023","journal-title":"Pathogens"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5660","DOI":"10.1038\/s41467-020-19464-8","article-title":"Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers","volume":"11","author":"Saini","year":"2020","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1002\/ajh.26822","article-title":"Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management","volume":"98","author":"Shimony","year":"2023","journal-title":"Am. J. Hematol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1158\/2159-8290.cd-19-1011","article-title":"Advances in the treatment of acute myeloid leukemia: new drugs and new challenges","volume":"10","author":"Short","year":"2020","journal-title":"Cancer Discovery"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00059-23","article-title":"CancerHERVdb: human endogenous retrovirus (HERV) expression database for human cancer accelerates studies of the retrovirome and predictions for HERV-based therapies","author":"Stricker","year":"2023","journal-title":"J. Virol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11030936","article-title":"HERVs and cancer-A comprehensive review of the relationship of human endogenous retroviruses and human cancers","volume":"11","author":"Stricker","year":"2023","journal-title":"Biomedicines"},{"key":"B32","doi-asserted-by":"publisher","first-page":"12565","DOI":"10.1073\/pnas.1814589115","article-title":"ERVmap analysis reveals genome-wide transcription of human endogenous retroviruses","volume":"115","author":"Tokuyama","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B33","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1128\/mmbr.00033-07","article-title":"Human RNA \"rumor\" viruses: the search for novel human retroviruses in chronic disease","volume":"72","author":"Voisset","year":"2008","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1158\/1078-0432.ccr-20-3417","article-title":"An immune risk score predicts survival of patients with acute myeloid leukemia receiving chemotherapy","volume":"27","author":"Wang","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2019.1683347","article-title":"The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia","volume":"9","author":"Xu","year":"2020","journal-title":"Oncoimmunology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1056\/NEJMc1713444","article-title":"Tumor mutational burden and response rate to PD-1 inhibition","volume":"377","author":"Yarchoan","year":"2017","journal-title":"N Engl. J. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1038\/ncomms3612","article-title":"Inferring tumour purity and stromal and immune cell admixture from expression data","volume":"4","author":"Yoshihara","year":"2013","journal-title":"Nat. Commun."},{"key":"B38","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12916-021-02047-9","article-title":"The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia","volume":"19","author":"Zeng","year":"2021","journal-title":"BMC Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"W234","DOI":"10.1093\/nar\/gkz240","article-title":"NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis","volume":"47","author":"Zhou","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1339673\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T04:39:41Z","timestamp":1704947981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1339673\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,11]]},"references-count":39,"alternative-id":["10.3389\/fcimb.2023.1339673"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1339673","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,11]]},"article-number":"1339673"}}