{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:44:44Z","timestamp":1790181884722,"version":"4.1.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["8236080196"],"award-info":[{"award-number":["8236080196"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["31900681"],"award-info":[{"award-number":["31900681"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation of Guangxi","award":["2022GXNSFAA035510"],"award-info":[{"award-number":["2022GXNSFAA035510"]}]},{"name":"National Science Foundation of Guangxi","award":["2023GXNSFAA026201"],"award-info":[{"award-number":["2023GXNSFAA026201"]}]},{"DOI":"10.13039\/501100002858","name":"Postdoctoral Science Foundation of China","doi-asserted-by":"crossref","award":["2021M693803"],"award-info":[{"award-number":["2021M693803"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Extensive evidence links <jats:italic>Clonorchis sinensis<\/jats:italic> (<jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic>) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection and HCC and reveal the relationship between <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection and cancer stemness.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A comprehensive analysis of 839 HCC patients categorized into <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (-) HCC and <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (+) HCC groups was conducted. Chi-square and Mann\u2013Whitney U tests were used to assess the association between <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection and clinical factors. Kaplan\u2013Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared to <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (-) HCC patients, <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19\u20139 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection correlated with shorter overall survival (OS) (<jats:italic>p<\/jats:italic> &lt; 0.05) and recurrence-free survival (RFS) (<jats:italic>p<\/jats:italic> &lt; 0.05). Furthermore, Cox multivariate analysis revealed that <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection was an independent prognostic factor for OS in HCC patients. Importantly, <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>HCC patients with <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection exhibit a poor prognosis following hepatectomy. Moreover, <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Author summary<\/jats:title>\n<jats:p><jats:italic>Clonorchis sinensis<\/jats:italic> (<jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic>) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> to cholangiocarcinoma, However, the connection between <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> and HCC, shedding fresh light on the carcinogenic potential of <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011906","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T18:21:24Z","timestamp":1706552484000},"page":"e0011906","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2845-3004","authenticated-orcid":true,"given":"Qiumei","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeli","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueling","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caibiao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengfei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingzheng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7336-9606","authenticated-orcid":true,"given":"Min","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"issue":"5","key":"pntd.0011906.ref001","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1053\/j.gastro.2023.01.033","article-title":"Global 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