{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:13:48Z","timestamp":1783091628905,"version":"3.54.6"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"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":["82360410, 2024GXNSFAA010212, 2023GXNSFAA026201,2022GXNSFAA035510"],"award-info":[{"award-number":["82360410, 2024GXNSFAA010212, 2023GXNSFAA026201,2022GXNSFAA035510"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"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><jats:italic>Clonorchis sinensis<\/jats:italic> (<jats:italic>C. sinensis<\/jats:italic>) infection plays an important role in the progression of hepatocarcinogenesis. However, its specific role in HCC progression remains unclear. This study aimed to investigate whether <jats:italic>C. sinensis<\/jats:italic> contributes to angiogenesis in HCC.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A comprehensive clinical analysis was conducted on 947 HCC patients, divided into two groups: <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (-) HCC and <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (+) HCC. Kaplan\u2013Meier survival curves and log-rank tests were utilized to assess survival outcomes. Microvessel density (MVD) was evaluated through CD34 immunohistochemistry on hepatectomy specimens. A chemistry analyzer and blood analyzer were employed to measure the concentration of circulating angiogenesis-related biomarkers. Quantitative reverse transcription-PCR (qRT-PCR) was used to analyze the expression of angiogenesis-related genes (CD34, Ang1, Ang2, VEGF, PDGF) in HCC tissues.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p><jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection was associated with poorer outcomes in HCC patients, with significantly shorter overall survival (OS) (<jats:italic>p<\/jats:italic> = 0.014) and recurrence-free survival (RFS) (<jats:italic>p<\/jats:italic>&lt;0.001). Notably, <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection led to an upregulation of MVD in HCC tissues (<jats:italic>p<\/jats:italic> = 0.041). <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (+) HCC patients exhibited significantly higher levels of circulating angiogenesis-related biomarkers, including MONO (<jats:italic>p<\/jats:italic> = 0.004), EOSO (<jats:italic>p<\/jats:italic> &lt; 0.001), C3 (<jats:italic>p<\/jats:italic> = 0.001), FIB (<jats:italic>p<\/jats:italic> = 0.010), PLT (<jats:italic>p<\/jats:italic> = 0.003), LDH (<jats:italic>p<\/jats:italic> = 0.004), GLDH (<jats:italic>p<\/jats:italic> = 0.003), compared to <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> (-) HCC patients. Moreover, qRT-PCR analysis revealed that most angiogenesis-related genes were overexpressed in patients with <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p><jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection is closely associated with inflammatory responses and may promote metabolic reprogramming in HCC, thereby enhancing its malignant characteristics.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012638","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T18:40:59Z","timestamp":1731350459000},"page":"e0012638","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Clonorchis sinensis infection contributes to hepatocellular carcinoma progression via enhancing 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