{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T22:52:49Z","timestamp":1784933569106,"version":"3.55.0"},"reference-count":78,"publisher":"Baishideng Publishing Group Inc.","issue":"32","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n          <jats:p>Hepatocellular carcinoma (HCC) is a global health concern, representing the second most common cause of malignancy-related mortality in the world. The primary cause of HCC in the United States is chronic infection with the hepatitis C virus (HCV). Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females, suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC. However, the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.<\/jats:p>\n          <jats:p>AIM<\/jats:p>\n          <jats:p>To determine whether estrogen receptor (ER) expression is correlated with the expression of tumor necrosis factor-alpha (TNF-\u03b1) in males and females with HCV-associated diseases.<\/jats:p>\n          <jats:p>METHODS<\/jats:p>\n          <jats:p>The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV\/cirrhosis and HCV\/HCC. Messenger RNA (mRNA) and protein (nuclear and cytoplasmic) expression were measured for all markers of interest and compared to normal human liver tissue samples.<\/jats:p>\n          <jats:p>RESULTS<\/jats:p>\n          <jats:p>ER\u03b2 was reported for the first time to have a greater mRNA expression than ER\u03b1 in normal liver (P  \u2264 0.001). In addition, ER\u03b2 mRNA expression was found to be decreased in diseased livers (P  \u2264 0.05), while TNF-\u03b1 expression was increased (P  \u2264 0.0001). Upon stratifying by sex within each disease group, ESR1  was found to be negatively correlated with ESR2  in females with HCV\/cirrhosis (r  = -0.84, P  \u2264 0.001), whereas males with HCV\/cirrhosis were found to have a significant positive correlation (r  = 0.57, P  \u2264 0.05). ESR2  mRNA expression had a significant positive correlation with TNF-\u03b1 in both HCV\/cirrhosis (r  = 0.61, P  \u2264 0.001) and HCV\/HCC patients (r  = 0.45, P  \u2264 0.05).<\/jats:p>\n          <jats:p>CONCLUSION<\/jats:p>\n          <jats:p>All together, these findings indicate that changes in ER\u03b2 and TNF-\u03b1 expression are associated with worsening disease, and may be part of the sex-dependent factors in HCC pathogenesis.<\/jats:p>","DOI":"10.3748\/wjg.v31.i32.104277","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T08:32:52Z","timestamp":1756197172000},"source":"Crossref","is-referenced-by-count":3,"title":["Sex based relative expression of estrogen receptors and tumor necrosis factor-alpha in liver affects hepatitis C virus viral pathogenesis"],"prefix":"10.3748","volume":"31","author":[{"given":"Sarah","family":"Groover","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Addison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Nicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchelle","family":"Mwangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e3182872f29"},{"key":"B2","unstructured":"United States Cancer Statistics.   About the U.S. Cancer Statistics Data Visualizations Tool. [cited July 1, 2025]. Available from: https:\/\/www.cdc.gov\/united-states-cancer-statistics\/dataviz\/index.html"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30297"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.031"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198612183152503"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811193392101"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i42.11984"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310236"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/s0168-8278(00)00097-0"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000567"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29936"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.5945"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.hep.2003.09.041"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20463"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.101931"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.12.027"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.05.036"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650050912"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/s8756-3282(01)00468-9"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.7.8919"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2010.00268.x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145212"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13303"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i37.6802"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2011.10.001"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.169"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2006.00767.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25726"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-243"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2010.02374.x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2013.06.005"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201600189"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2018.01.015"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/path.2277"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.010"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(96)07642-8"},{"key":"B37","doi-asserted-by":"crossref","unstructured":"Chiaramonte M, Stroffolini T, Vian A, Stazi MA, Floreani A, Lorenzoni U, Lobello S, Farinati F, Naccarato R. Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 1999; 2132-2137","DOI":"10.1002\/(SICI)1097-0142(19990515)85:10<2132::AID-CNCR6>3.3.CO;2-8"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.04.061"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k2817"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.763539"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1140485"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.348763"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.08.012"},{"key":"B44","doi-asserted-by":"crossref","unstructured":"Kilbourne EJ, Scicchitano MS. The activation of plasminogen activator inhibitor-1 expression by IL-1beta is attenuated by estrogen in hepatoblastoma HepG2 cells expressing estrogen receptor alpha. Thromb Haemost 1999; 423-427","DOI":"10.1055\/s-0037-1614489"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/gut.44.1.127"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290307"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11528"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/s0959-8049(01)00383-5"},{"key":"B49","unstructured":"Dove LM, Brown RS, Jr.   Liver transplantation in adults: Patient selection and pretransplantation evaluation. In: Post TW, editor. UpToDate. Waltham, MA: UpToDate, 2020"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-018-0116-7"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon.21885"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0676.2001.210507.x"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13102355"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2013.08.006"},{"key":"B55","unstructured":"Villa E, Camellini L, Dugani A, Zucchi F, Grottola A, Merighi A, Buttafoco P, Losi L, Manenti F. Variant estrogen receptor messenger RNA species detected in human primary hepatocellular carcinoma. Cancer Res 1995; 498-500"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270413"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2006.47.6.811"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2010.0108"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23469"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i13.2065"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.1.0456"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.216037"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.15.3505"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203828"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0206"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2005.04.008"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.09.019"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0381"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2521"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit433"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit827"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.06.035"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3505"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210712"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0252"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-017-0298-1"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1433540"}],"container-title":["World Journal of Gastroenterology"],"original-title":[],"link":[{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v31\/i32\/104277.htm","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v31\/i32\/104277.htm","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T08:32:53Z","timestamp":1756197173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v31\/i32\/104277.htm"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":78,"journal-issue":{"issue":"32"},"alternative-id":["104277"],"URL":"https:\/\/doi.org\/10.3748\/wjg.v31.i32.104277","relation":{},"ISSN":["1007-9327"],"issn-type":[{"value":"1007-9327","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8,28]]}}}