{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T18:07:05Z","timestamp":1769969225796,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Research and Innovation Fund"},{"DOI":"10.13039\/501100004704","name":"the National Research Council of Thailand","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010034","name":"Walailak University","doi-asserted-by":"crossref","award":["WU69226"],"award-info":[{"award-number":["WU69226"]}],"id":[{"id":"10.13039\/501100010034","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Cholangiocarcinoma (CCA) is a very aggressive biliary carcinoma characterised by significant molecular heterogeneity and restricted treatment alternatives. Despite genomic and proteomic investigations revealing recurrent changes, the signalling dynamics influencing tumour behaviour remain inadequately comprehended. Methods: We conducted high-resolution Liquid Chromatography\u2013Tandem Mass Spectrometry (LC\u2013MS\/MS)-based phosphoproteomics on paired tumour and surrounding tissues from 13 CCA patients in Northeast Thailand, meticulously sampling four geographically unique tumour areas for each patient. Our analysis concentrated on phosphoproteins consistently identified across all regions, delineating strong tumour-specific and cohort-wide phosphorylation signatures. Results: Notwithstanding considerable inter-patient variability, two conserved signalling modules were identified: an adhesion\/Wnt axis regulated by hyperphosphorylated CTNNB1 protein (\u03b2-catenin) and a metal-handling module facilitated by metallothionein-1G (MT1G) protein and metallothionein-2A (MT2A) protein. Pathway enrichment identified focal adhesion, ECM-receptor interaction, cytoskeletal modulation, and mineral absorption as critical activities. Conclusions: This study elucidates conserved oncogenic pathways by analysing phosphoproteomic signatures across regional and patient-level variability, emphasising phosphoproteomics as a robust framework for biomarker and therapeutic development in CCA.<\/jats:p>","DOI":"10.3390\/medsci14010063","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:38:34Z","timestamp":1769794714000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conserved Phosphoprotein Networks Identify Actionable Adhesion\/Wnt and Metallothionein Modules in Cholangiocarcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2939-1706","authenticated-orcid":false,"given":"Sirinya","family":"Sitthirak","sequence":"first","affiliation":[{"name":"Department of Medical Technology, School of Allied Health Sciences, Walailak University, 222 Thaiburi, Thasala District, Nakhon Si Thammarat 80161, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-8390","authenticated-orcid":false,"given":"Sittiruk","family":"Roytrakul","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4536-4492","authenticated-orcid":false,"given":"Arporn","family":"Wangwiwatsin","sequence":"additional","affiliation":[{"name":"Department of Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6743-5047","authenticated-orcid":false,"given":"Nisana","family":"Namwat","sequence":"additional","affiliation":[{"name":"Department of Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-3901","authenticated-orcid":false,"given":"Poramate","family":"Klanrit","sequence":"additional","affiliation":[{"name":"Department of Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4765-333X","authenticated-orcid":false,"given":"Hasaya","family":"Dokduang","sequence":"additional","affiliation":[{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prakasit","family":"Sa-ngiamwibool","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attapol","family":"Titapun","sequence":"additional","affiliation":[{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apiwat","family":"Jareanrat","sequence":"additional","affiliation":[{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasin","family":"Thanasukarn","sequence":"additional","affiliation":[{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6689-2525","authenticated-orcid":false,"given":"Natcha","family":"Khuntikeo","sequence":"additional","affiliation":[{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teh Bin","family":"Tean","sequence":"additional","affiliation":[{"name":"National Cancer Centre Singapore, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke","family":"Boulter","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8572-5577","authenticated-orcid":false,"given":"Watcharin","family":"Loilome","sequence":"additional","affiliation":[{"name":"Department of Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: The next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat. 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