Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis
Extensive evidence links Clonorchis sinensis (C. sinensis) 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 C. sinensis infection and...
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| creator | Lin, Qiumei Tang, Zeli Qin, Yuling Deng, Xueling Wei, Caibiao Liu, Fengfei Pan, Xiaolan Liu, Dengyu Zhan, Tingzheng Fang, Min |
| description | Extensive evidence links Clonorchis sinensis (C. sinensis) 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 C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.
A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.
Compared to C. sinensis (-) HCC patients, C. sinensis (+) 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 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.
HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.
Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, |
| doi_str_mv | 10.1371/journal.pntd.0011906 |
| format | Article |
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A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.
Compared to C. sinensis (-) HCC patients, C. sinensis (+) 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 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.
HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.
Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis 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 C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis 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 C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0011906</identifier><identifier>PMID: 38285640</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>alpha-Fetoproteins - analysis ; alpha-Fetoproteins - metabolism ; Animals ; Antigens ; Bile Duct Neoplasms ; Bile ducts ; Bile Ducts, Intrahepatic - chemistry ; Bile Ducts, Intrahepatic - metabolism ; Bile Ducts, Intrahepatic - pathology ; Biology and Life Sciences ; CA-19-9 Antigen ; Cancer ; Cancer therapies ; Carbohydrates ; Carcinogens ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - surgery ; Cardiovascular disease ; Care and treatment ; China - epidemiology ; Cholangiocarcinoma ; Cirrhosis ; Clonorchiasis - complications ; Clonorchis sinensis ; Clonorchis sinensis - metabolism ; Complement component C3 ; Complement component C4 ; Data collection ; Eosinophils ; Epithelial Cell Adhesion Molecule ; Ethics ; Fibrosis ; Gender ; Hematology ; Hepatectomy ; Hepatitis ; Hepatocellular carcinoma ; Hepatoma ; Hospitals ; Humans ; Immunohistochemistry ; Infections ; Leukocytes (eosinophilic) ; Liver cancer ; Liver cirrhosis ; Liver Cirrhosis - pathology ; Liver Neoplasms - complications ; Liver Neoplasms - pathology ; Lymphocytes ; Male ; Medical prognosis ; Medicine and Health Sciences ; Metastasis ; Mortality ; Multivariate analysis ; Neoplasm Staging ; Neoplasms ; Parasites ; Patient outcomes ; Patients ; Prognosis ; Regression analysis ; Retrospective Studies ; Risk factors ; Sialyl Lewis a antigen ; Statistical analysis ; Stem cells ; Survival ; Tumors ; α-Fetoprotein</subject><ispartof>PLoS neglected tropical diseases, 2024-01, Vol.18 (1), p.e0011906</ispartof><rights>Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Lin et al 2024 Lin et al</rights><rights>2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c574t-44fe2681076df8c60798fb6e7b4b88082edbfa6f8daeeb760277a166495ae4623</cites><orcidid>0009-0008-7336-9606 ; 0000-0003-2845-3004</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824460/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824460/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38285640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Smout, Michael J.</contributor><creatorcontrib>Lin, Qiumei</creatorcontrib><creatorcontrib>Tang, Zeli</creatorcontrib><creatorcontrib>Qin, Yuling</creatorcontrib><creatorcontrib>Deng, Xueling</creatorcontrib><creatorcontrib>Wei, Caibiao</creatorcontrib><creatorcontrib>Liu, Fengfei</creatorcontrib><creatorcontrib>Pan, Xiaolan</creatorcontrib><creatorcontrib>Liu, Dengyu</creatorcontrib><creatorcontrib>Zhan, Tingzheng</creatorcontrib><creatorcontrib>Fang, Min</creatorcontrib><title>Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Extensive evidence links Clonorchis sinensis (C. sinensis) 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 C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.
A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.
Compared to C. sinensis (-) HCC patients, C. sinensis (+) 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 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.
HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.
Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis 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 C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis 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 C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.</description><subject>alpha-Fetoproteins - analysis</subject><subject>alpha-Fetoproteins - metabolism</subject><subject>Animals</subject><subject>Antigens</subject><subject>Bile Duct Neoplasms</subject><subject>Bile ducts</subject><subject>Bile Ducts, Intrahepatic - chemistry</subject><subject>Bile Ducts, Intrahepatic - metabolism</subject><subject>Bile Ducts, Intrahepatic - pathology</subject><subject>Biology and Life Sciences</subject><subject>CA-19-9 Antigen</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carbohydrates</subject><subject>Carcinogens</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - surgery</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>China - epidemiology</subject><subject>Cholangiocarcinoma</subject><subject>Cirrhosis</subject><subject>Clonorchiasis - complications</subject><subject>Clonorchis sinensis</subject><subject>Clonorchis sinensis - metabolism</subject><subject>Complement component C3</subject><subject>Complement component C4</subject><subject>Data collection</subject><subject>Eosinophils</subject><subject>Epithelial Cell Adhesion Molecule</subject><subject>Ethics</subject><subject>Fibrosis</subject><subject>Gender</subject><subject>Hematology</subject><subject>Hepatectomy</subject><subject>Hepatitis</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatoma</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Infections</subject><subject>Leukocytes (eosinophilic)</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis - pathology</subject><subject>Liver Neoplasms - complications</subject><subject>Liver Neoplasms - pathology</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Metastasis</subject><subject>Mortality</subject><subject>Multivariate analysis</subject><subject>Neoplasm Staging</subject><subject>Neoplasms</subject><subject>Parasites</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Regression analysis</subject><subject>Retrospective Studies</subject><subject>Risk factors</subject><subject>Sialyl Lewis a antigen</subject><subject>Statistical analysis</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Tumors</subject><subject>α-Fetoprotein</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1rFDEUHUSxtfoPRAcE8cFdk8nnPJWy-FEo-KLPIZPc2U3NJGsyU_Dfm3GnZVdKHnK5Oefcj5yqeo3RGhOBP93GKQXt1_sw2jVCGLeIP6nOcUvYqhGEPT2Kz6oXOd8ixFom8fPqjMhGMk7RefVr42OIyexcrrMLEHIJXOjBjC6GWg9773oHud7BXo_RgPeT16k2OhkX4qDrPMIQIOeP9T6BdYUXtvUUen0Xk-48lHTchlh0X1bPeu0zvFrui-rnl88_Nt9WN9-_Xm-ublaGCTquKO2h4RIjwW0vDUeilX3HQXS0kxLJBmzXa95LqwE6wVEjhMac05ZpoLwhF9Xbg-7ex6yWPWVFEG-xJJTRgrg-IGzUt2qf3KDTHxW1U_8SMW2VTqMzHpThgjJmQGorqGWkY4RbbiUlQmLJedG6XKpN3QDWQBiT9ieipy_B7dQ23ilcRqGUo6LwYVFI8fcEeVSDy_OmdYA4ZdW0DcJSUDxD3_0HfXy8BbXVZYLym7EUNrOouipdN1QQOWutH0GVY2FwJgboXcmfEN4fEXag_bjL0U-zU_IpkB6AJsWcE_QP28BIzea971rN5lWLeQvtzfEmH0j3biV_AXwd7VQ</recordid><startdate>20240101</startdate><enddate>20240101</enddate><creator>Lin, Qiumei</creator><creator>Tang, Zeli</creator><creator>Qin, Yuling</creator><creator>Deng, Xueling</creator><creator>Wei, Caibiao</creator><creator>Liu, Fengfei</creator><creator>Pan, Xiaolan</creator><creator>Liu, Dengyu</creator><creator>Zhan, Tingzheng</creator><creator>Fang, Min</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0009-0008-7336-9606</orcidid><orcidid>https://orcid.org/0000-0003-2845-3004</orcidid></search><sort><creationdate>20240101</creationdate><title>Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis</title><author>Lin, Qiumei ; Tang, Zeli ; Qin, Yuling ; Deng, Xueling ; Wei, Caibiao ; Liu, Fengfei ; Pan, Xiaolan ; Liu, Dengyu ; Zhan, Tingzheng ; Fang, Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c574t-44fe2681076df8c60798fb6e7b4b88082edbfa6f8daeeb760277a166495ae4623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>alpha-Fetoproteins - analysis</topic><topic>alpha-Fetoproteins - metabolism</topic><topic>Animals</topic><topic>Antigens</topic><topic>Bile Duct Neoplasms</topic><topic>Bile ducts</topic><topic>Bile Ducts, Intrahepatic - chemistry</topic><topic>Bile Ducts, Intrahepatic - metabolism</topic><topic>Bile Ducts, Intrahepatic - pathology</topic><topic>Biology and Life Sciences</topic><topic>CA-19-9 Antigen</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Carbohydrates</topic><topic>Carcinogens</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - surgery</topic><topic>Cardiovascular disease</topic><topic>Care and treatment</topic><topic>China - epidemiology</topic><topic>Cholangiocarcinoma</topic><topic>Cirrhosis</topic><topic>Clonorchiasis - complications</topic><topic>Clonorchis sinensis</topic><topic>Clonorchis sinensis - metabolism</topic><topic>Complement component C3</topic><topic>Complement component C4</topic><topic>Data collection</topic><topic>Eosinophils</topic><topic>Epithelial Cell Adhesion Molecule</topic><topic>Ethics</topic><topic>Fibrosis</topic><topic>Gender</topic><topic>Hematology</topic><topic>Hepatectomy</topic><topic>Hepatitis</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatoma</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Infections</topic><topic>Leukocytes (eosinophilic)</topic><topic>Liver cancer</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis - pathology</topic><topic>Liver Neoplasms - complications</topic><topic>Liver Neoplasms - pathology</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Metastasis</topic><topic>Mortality</topic><topic>Multivariate analysis</topic><topic>Neoplasm Staging</topic><topic>Neoplasms</topic><topic>Parasites</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Regression analysis</topic><topic>Retrospective Studies</topic><topic>Risk factors</topic><topic>Sialyl Lewis a antigen</topic><topic>Statistical analysis</topic><topic>Stem cells</topic><topic>Survival</topic><topic>Tumors</topic><topic>α-Fetoprotein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Qiumei</creatorcontrib><creatorcontrib>Tang, Zeli</creatorcontrib><creatorcontrib>Qin, Yuling</creatorcontrib><creatorcontrib>Deng, Xueling</creatorcontrib><creatorcontrib>Wei, Caibiao</creatorcontrib><creatorcontrib>Liu, Fengfei</creatorcontrib><creatorcontrib>Pan, Xiaolan</creatorcontrib><creatorcontrib>Liu, Dengyu</creatorcontrib><creatorcontrib>Zhan, Tingzheng</creatorcontrib><creatorcontrib>Fang, Min</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Qiumei</au><au>Tang, Zeli</au><au>Qin, Yuling</au><au>Deng, Xueling</au><au>Wei, Caibiao</au><au>Liu, Fengfei</au><au>Pan, Xiaolan</au><au>Liu, Dengyu</au><au>Zhan, Tingzheng</au><au>Fang, Min</au><au>Smout, Michael J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2024-01-01</date><risdate>2024</risdate><volume>18</volume><issue>1</issue><spage>e0011906</spage><pages>e0011906-</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Extensive evidence links Clonorchis sinensis (C. sinensis) 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 C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.
A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.
Compared to C. sinensis (-) HCC patients, C. sinensis (+) 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 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.
HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.
Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis 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 C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis 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 C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>38285640</pmid><doi>10.1371/journal.pntd.0011906</doi><orcidid>https://orcid.org/0009-0008-7336-9606</orcidid><orcidid>https://orcid.org/0000-0003-2845-3004</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2024-01, Vol.18 (1), p.e0011906 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_3069183454 |
| source | PLoS; MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; PubMed (Medline); EZB Electronic Journals Library |
| subjects | alpha-Fetoproteins - analysis alpha-Fetoproteins - metabolism Animals Antigens Bile Duct Neoplasms Bile ducts Bile Ducts, Intrahepatic - chemistry Bile Ducts, Intrahepatic - metabolism Bile Ducts, Intrahepatic - pathology Biology and Life Sciences CA-19-9 Antigen Cancer Cancer therapies Carbohydrates Carcinogens Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - surgery Cardiovascular disease Care and treatment China - epidemiology Cholangiocarcinoma Cirrhosis Clonorchiasis - complications Clonorchis sinensis Clonorchis sinensis - metabolism Complement component C3 Complement component C4 Data collection Eosinophils Epithelial Cell Adhesion Molecule Ethics Fibrosis Gender Hematology Hepatectomy Hepatitis Hepatocellular carcinoma Hepatoma Hospitals Humans Immunohistochemistry Infections Leukocytes (eosinophilic) Liver cancer Liver cirrhosis Liver Cirrhosis - pathology Liver Neoplasms - complications Liver Neoplasms - pathology Lymphocytes Male Medical prognosis Medicine and Health Sciences Metastasis Mortality Multivariate analysis Neoplasm Staging Neoplasms Parasites Patient outcomes Patients Prognosis Regression analysis Retrospective Studies Risk factors Sialyl Lewis a antigen Statistical analysis Stem cells Survival Tumors α-Fetoprotein |
| title | Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis |
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