{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:20:20Z","timestamp":1790742020208,"version":"4.1.0"},"reference-count":95,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science, Research and Innovation Fund (NSRF)","award":["SCI6701131S"],"award-info":[{"award-number":["SCI6701131S"]}]},{"name":"National Science, Research and Innovation Fund (NSRF)","award":["PSU_PHD2561-001"],"award-info":[{"award-number":["PSU_PHD2561-001"]}]},{"name":"National Science, Research and Innovation Fund (NSRF)","award":["1-2565-02-023"],"award-info":[{"award-number":["1-2565-02-023"]}]},{"name":"Prince of Songkla University\u2014Ph.D. Scholarship","award":["SCI6701131S"],"award-info":[{"award-number":["SCI6701131S"]}]},{"name":"Prince of Songkla University\u2014Ph.D. Scholarship","award":["PSU_PHD2561-001"],"award-info":[{"award-number":["PSU_PHD2561-001"]}]},{"name":"Prince of Songkla University\u2014Ph.D. Scholarship","award":["1-2565-02-023"],"award-info":[{"award-number":["1-2565-02-023"]}]},{"name":"Graduate Fellowship (Research Assistant), Faculty of Science, Prince of Songkhla University","award":["SCI6701131S"],"award-info":[{"award-number":["SCI6701131S"]}]},{"name":"Graduate Fellowship (Research Assistant), Faculty of Science, Prince of Songkhla University","award":["PSU_PHD2561-001"],"award-info":[{"award-number":["PSU_PHD2561-001"]}]},{"name":"Graduate Fellowship (Research Assistant), Faculty of Science, Prince of Songkhla University","award":["1-2565-02-023"],"award-info":[{"award-number":["1-2565-02-023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Drug resistance is a major challenge in the treatment of advanced cholangiocarcinoma (CCA). Understanding the mechanisms of drug resistance can aid in identifying novel prognostic biomarkers and therapeutic targets to improve treatment efficacy. This study established 5-fluorouracil- (5-FU) and gemcitabine-resistant CCA cell lines, KKU-213FR and KKU-213GR, and utilized comparative proteomics to identify differentially expressed proteins in drug-resistant cells compared to parental cells. Additionally, bioinformatics analyses were conducted to explore the biological and clinical significance of key proteins. The drug-resistant phenotypes of KKU-213FR and KKU-213GR cell lines were confirmed. In addition, these cells demonstrated increased migration and invasion abilities. Proteomics analysis identified 81 differentially expressed proteins in drug-resistant cells, primarily related to binding functions, biological regulation, and metabolic processes. Protein\u2013protein interaction analysis revealed a highly interconnected network involving MET, LAMB1, ITGA3, NOTCH2, CDH2, and NDRG1. siRNA-mediated knockdown of these genes in drug-resistant cell lines attenuated cell migration and cell invasion abilities and increased sensitivity to 5-FU and gemcitabine. The mRNA expression of these genes is upregulated in CCA patient samples and is associated with poor prognosis in gastrointestinal cancers. Furthermore, the functions of these proteins are closely related to the epithelial\u2013mesenchymal transition (EMT) pathway. These findings elucidate the potential molecular mechanisms underlying drug resistance and tumor progression in CCA, providing insights into potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/biom14080969","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T09:48:54Z","timestamp":1723196934000},"page":"969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0536-0375","authenticated-orcid":false,"given":"Kankamol","family":"Kerdkumthong","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-8390","authenticated-orcid":false,"given":"Sittiruk","family":"Roytrakul","sequence":"additional","affiliation":[{"name":"Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Tani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kawinnath","family":"Songsurin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandawasri","family":"Pratummanee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phanthipha","family":"Runsaeng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand"},{"name":"Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-0563","authenticated-orcid":false,"given":"Sumalee","family":"Obchoei","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand"},{"name":"Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai District, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,8]]},"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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