{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:05:41Z","timestamp":1784250341562,"version":"3.55.0"},"reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373673"],"award-info":[{"award-number":["82373673"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370608"],"award-info":[{"award-number":["82370608"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFA1800800"],"award-info":[{"award-number":["2023YFA1800800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Education Department of Anhui Province","award":["2022AH040160"],"award-info":[{"award-number":["2022AH040160"]}]},{"name":"Anhui Provincial Special Fund for Clinical Medical Research Transformation","award":["202304295107020040"],"award-info":[{"award-number":["202304295107020040"]}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20240813151903006"],"award-info":[{"award-number":["JCYJ20240813151903006"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Portal vein tumor thrombus is a lethal complication of HCC for which effective biomarkers are urgently needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Through proteomic profiling, functional and mechanistic assays, and machine learning-based evaluation of serum NSUN6 in 472 HCC patients with external validation (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200998), we characterized an epitranscriptomic regulator of HCC metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NSUN6 was downregulated in PVTT and suppressed metastasis by catalyzing m\u2075C modification of\n                      <jats:italic>SAV1<\/jats:italic>\n                      mRNA, stabilizing its transcript and activating Hippo signaling. Furthermore, NSUN6 was released from HCC cells via extracellular vesicle-associated and non-canonical pathways. Circulating NSUN6 levels were inversely associated with metastasis in both discovery and validation cohorts, and lower levels predicted shorter metastasis-free survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings establish the NSUN6\u2013SAV1\u2013YAP axis as a key epitranscriptomic tumor-suppressive mechanism and support circulating NSUN6 as a potential biomarker for early risk stratification in HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-026-03786-4","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:46:44Z","timestamp":1784249204000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating NSUN6 serves as a prognostic biomarker for early metastasis in HCC via hippo pathway modulation"],"prefix":"10.1186","author":[{"given":"Xutong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yani","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhu","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwan","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shucheng","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutterodt","family":"Bentum-Ennin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanglai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanshui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-026-03786-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:46:45Z","timestamp":1784249205000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13046-026-03786-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":0,"alternative-id":["3786"],"URL":"https:\/\/doi.org\/10.1186\/s13046-026-03786-4","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"3 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The animal study followed ARRIVE 2.0 guidelines, with a pre-established protocol, and was approved by the Animal Research Ethics Committee of Anhui Medical University (No. LLSC20240919). The institutional review board of Anhui Medical University and No.2 People\u2019s Hospital of Fuyang City approved the study (No. 20210728 and No. 20250415113). All procedures involving human participants were performed in accordance with the Declaration of Helsinki and written informed consent was obtained from all patients.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}