{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T23:00:00Z","timestamp":1774393200229,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T00:00:00Z","timestamp":1683331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Although the roles of erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuregulin 4 (NRG4), and mitogen-inducible gene 6 (MIG6) in epidermal growth factor receptor signaling in hepatocellular carcinoma (HCC) and other malignancies have been previously investigated, the prognostic value of their serum levels in HCC remains undetermined. In the present study, correlations between serum levels and tumor characteristics, overall survival, and tumor recurrence were analyzed. Furthermore, the prognostic potential of the serum levels of these biomarkers was evaluated relative to that of alpha-fetoprotein. Both ERBB2 and NRG4 correlated with the Barcelona Clinic Liver Cancer stage, ERBB2 correlated with the tumor-maximal diameter, and NRG4 correlated with a tumor number. Cox proportional hazards regression analysis revealed that ERBB2 (hazard ratio [HR], 2.719; p = 0.007) was an independent prognostic factor for overall survival. Furthermore, ERBB2 (HR, 2.338; p = 0.002) and NRG4 (HR, 431.763; p = 0.001) were independent prognostic factors for tumor recurrence. The products of ERBB2 and NRG4 had a better area under the curve than alpha-fetoprotein for predicting 6-month, 1-year, 3-year, and 5-year mortality. Therefore, these factors could be used to evaluate prognosis and monitor treatment response in patients with HCC.<\/jats:p>","DOI":"10.3390\/cancers15092634","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T02:03:31Z","timestamp":1683511411000},"page":"2634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prognostic Value of Erythroblastic Leukemia Viral Oncogene Homolog 2 and Neuregulin 4 in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1619-2660","authenticated-orcid":false,"given":"Woo Sun","family":"Rou","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong 30099, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0485-0072","authenticated-orcid":false,"given":"Hyuk Soo","family":"Eun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sorim","family":"Choung","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Jae","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong 30099, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Seok","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong 30099, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun Hyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eaum Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seok Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Sun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Statistics Office, Biomedical Research Institute, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3414-8949","authenticated-orcid":false,"given":"Bon Jeong","family":"Ku","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Endocrinology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea"},{"name":"Division of Gastroenterology and 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