{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T11:10:03Z","timestamp":1749553803931,"version":"3.41.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Frankfurt"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>The newly discovered histone methyltransferase KMT9 serves as an epigenetic regulator of carcinogenesis in various cancer entities. For the first time, we investigated the presence of KMT9\u03b1 in cholangiocarcinoma, the association with histologic subtypes, and its impact on survival.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A tissue microarray cohort of all CCA patients who underwent surgical resection with curative intent between 08\/2005 and 12\/2021 at the University Hospital Frankfurt was immunohistochemically analyzed with the KMT9\u03b1 antibody. For overall survival, Kaplan\u2013Meier curves and Cox-regression analyses were performed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In total, 174 patients were suitable for IHC analysis. Of the patients, 35.1% (<jats:italic>n<\/jats:italic>\u2009=\u200961) overexpressed KMT9\u03b1. Kaplan-Meier curves revealed a median OS of 34.75 months (95% CI\u2009=\u200920.23\u201349.27 months) for all CCA patients positive for KMT9\u03b1 in comparison to 54.21 months (95% CI\u2009=\u200941.78\u201366.63 months) for patients lacking KMT9\u03b1 overexpression (<jats:italic>p<\/jats:italic>\u2009=\u20090.004). Subtype analysis revealed strong differences in KMT9\u03b1 expression. Multivariate Cox regression analysis identified KMT9\u03b1 as an independent risk factor for shorter OS in CCA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study demonstrates that a marked subset of CCA patients exhibit overexpression of KMT9\u03b1. These findings underscore the prognostic significance of KMT9\u03b1 and reinforce its potential as a therapeutic target, consistent with its role in other cancer types.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00432-025-06214-w","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T01:54:53Z","timestamp":1747101293000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Overexpression of KMT9\u03b1 is associated with poor outcome in cholangiocarcinoma patients"],"prefix":"10.1007","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-1455","authenticated-orcid":false,"given":"Maximilian N.","family":"Kinzler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1394-1083","authenticated-orcid":false,"given":"Eric","family":"Metzger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Bankov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0031-4103","authenticated-orcid":false,"given":"Anna","family":"Ramos-Triguero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Falko","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Gretser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nada","family":"Abedin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Wiegering","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0845-6833","authenticated-orcid":false,"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-9624","authenticated-orcid":false,"given":"Dirk","family":"Walter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1373-5295","authenticated-orcid":false,"given":"Henning","family":"Reis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Sch\u00fcle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Wild","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"6214_CR1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/jhbp.154","volume":"22","author":"S Aishima","year":"2015","unstructured":"Aishima S, Oda Y (2015) Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of Perihilar large duct type versus peripheral small duct type. 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The study was performed in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Patients provided informed written consent and patient data was provided after approval by the local ethics committee.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"S. Z.: Consultancy and\/or speaker\u2019s bureau: Abbvie, Boehringer Ingelheim, Gilead, GSK, Ipsen, Madrigal, MSD, NovoNordisk; H.R.: Received honoraria from Astellas, Astra-Zeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, CHOP GmbH, Diaceutics, Evidia, GlaxoSmithKline, HUeG e.V., Janssen-Cilag, Klinikum Wolfsburg, MCI, Menarini Stemline, Merck, Novartis, Roche, Sanofi, and Takeda, and received travel support from Philips, Roche, and Bristol-Myers Squibb, and received grants from Bristol-Myers Squibb, and holds shares of AstraZeneca. P.J.W.: Consulting fees and honoraria for lectures from Bayer, Sanofi, Novartis, Roche, MSD, Astellas Pharma, Bristol-Myers Squibb, Thermo Fisher Scientific, Molecular Health, Guardant Health, Eli Lilly, Menarini Group, Myriad, Hedera Dx, and AstraZeneca. Research support was provided by AstraZeneca, iOMEDICO, and Roche. The authors declare that there is no relationship relevant to the manuscripts\u2019 subject. All other authors declare no conflicts of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"161"}}