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Tumor-specific biomarkers are required for mUM patients to monitor early disease progression on immunotherapies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We investigated clinical characteristics such as liver tumor burden and routine blood tumor markers, including lactate dehydrogenase (LDH) and transaminases in patients with mUM and with liver metastasized cutaneous melanoma (LmCM), treated with immune checkpoint inhibitors (ICIs) between May 2013-February 2024. In addition, we analyzed soluble cMET (scMET) in serum samples from these patients along with a cohort of mCM patients without liver metastases (nLmCM) using ELISA. Circulating tumor DNA (ctDNA) in the plasma was analyzed using digital droplet PCR (ddPCR) in mUM patients receiving immunotherapies. scMET, ctDNA, and LDH combination was used to simultaneously monitor disease progression in ICI and tebentafusp-receiving mUM patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Sixty-nine patients with mUM and seventy-six patients with LmCM were treated with either anti-PD1 monotherapy (<jats:italic>n<\/jats:italic>\u2009=\u200969, 48%) or ipi\u2009+\u2009nivo combination therapy (<jats:italic>n<\/jats:italic>\u2009=\u200976, 52%). Irrespective of the type of melanoma and type of immunotherapy, patients with liver metastasis size greater than 8cm experienced rapid disease progression. ICI-treated mUM patients with increased LDH, aspartate aminotransferase (AST), alanine transaminase (ALT), scMET, ctDNA, and rapidly growing tumors were significantly associated with treatment resistance and shorter progression-free and overall survival (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). scMET (AUC: 0.82) outperforms LDH (AUC: 0.77) and S100 (0.68) in predicting one-year overall survival in these patients. A validation set with LmCM and nLmCM patient samples showed that increased scMET is likely a mUM-specific feature and does not predict ICI outcomes in LmCM or nLmCM patients (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). Moreover, monitoring ctDNA and scMET in mUM patients under ICIs or tebentafusp treatment revealed the potential for early detection of disease progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Soluble cMET might serve as a tumor-specific biomarker to predict clinical outcomes in mUM patients. A combinational assessment of scMET and ctDNA in mUM patients\u2019 blood offers a highly sensitive potential approach to monitor early disease progression under immunotherapies with ICI or tebentafusp.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13046-025-03451-2","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T02:45:37Z","timestamp":1752893137000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies"],"prefix":"10.1186","volume":"44","author":[{"given":"Devayani","family":"Machiraju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian H","family":"Ziener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Clementi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Garc\u00eda-Asencio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"H\u00fcllein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Lenoir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Wiecken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"H\u00fcbschmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"J\u00e4ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C","family":"Hassel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"3451_CR1","doi-asserted-by":"publisher","unstructured":"van der Kooij MK, Speetjens FM, van der Burg SH, Kapiteijn E. 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Journal of Clinical Oncology. 2021.","DOI":"10.1200\/JCO.2021.39.15_suppl.9535"}],"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03451-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-025-03451-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03451-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T15:02:17Z","timestamp":1752937337000},"score":1,"resource":{"primary":{"URL":"https:\/\/jeccr.biomedcentral.com\/articles\/10.1186\/s13046-025-03451-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,19]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3451"],"URL":"https:\/\/doi.org\/10.1186\/s13046-025-03451-2","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,19]]},"assertion":[{"value":"17 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All clinical records were obtained with the approval of the Institutional Review Board (S-454\/2015), and patients\u2019 consents were obtained for scientific biobanking of peripheral blood (S-207\/2005). MASTER study received Institutional Review Board approval from the Ethics Committee (Medical Faculty of Heidelberg University, reference number: S-206\/2011.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"JCH has received honoraria from BMS, MSD, Novartis, Roche, Pierre Fabre, Sanofi, Almirall; consult-ant or advisory role: MSD, Pierre Fabre, Sunpharma; research funding: BMS; travel support: Pierre Fabre. DJ has received payment or honoraria from MSD, BMS, Roche, The Norwegian Cancer Society, Center for Modern Hospital Management Bejing, Gruppe 4 Filmproduktion GmbH, Centrum f\u00fcr integrierte Onkologie, Dept of Radiation Medicine; consultant or advisory role: OncoOne, CureVac, Amgen, Roche; travel support: BMS, CureVac, Amgen, Parexel, BCPPC, Berlin Institute of Health, Oncogenics, ForTra gGmbH, Pancreas Center Karolinska Institute of Sweden, Centrum f\u00fcr integrierte Onkologie, Bioevents-congress.com. EC and FG are employees of Oncobit company. DM, CZ, JH, BL, JR, MW, and DH declared no conflicts of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"213"}}