{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:22:31Z","timestamp":1783646551849,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA237327"],"award-info":[{"award-number":["CA237327"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102016M3A9D5A01952416"],"award-info":[{"award-number":["NRF\u20102016M3A9D5A01952416"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102020R1A2B5B01001646"],"award-info":[{"award-number":["NRF\u20102020R1A2B5B01001646"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Late recurrence of hepatocellular carcinoma (HCC) is regarded as de novo HCC from chronic hepatitis. This study investigated clinicopathological and molecular factors to develop a nomogram for predicting late HCC recurrence (&gt;2\u00a0years after curative resection).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The training and validation cohorts included HCC patients with a major aetiology of hepatitis B who underwent curative resection. Clinicopathological features including lobular and porto\u2010periportal inflammatory activity, fibrosis and liver cell change were evaluated. Proteins encoded by genes related to late recurrence were identified using a reverse phase protein array of 95 non\u2010tumourous liver tissues. Immunoexpression of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), plasminogen activator inhibitor\u20101, phosphorylated extracellular signal\u2010regulated kinase 1\/2 (pERK1\/2) and spleen tyrosine kinase (SYK) was measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Late recurrence occurred in 74\/402 (18%) and 47\/243 (19%) in the training and validation cohorts respectively. Cirrhosis, moderate\/severe lobular inflammatory activity, and expression of pSTAT3, pERK1\/2, and SYK proteins correlated to the gene signature of hepatocyte injury and regeneration were independently associated with late recurrence, with odds ratios (95% confidence intervals) of 2.0 (1.2\u20103.3), 21.1 (4.3\u2010102.7) and 6.0 (2.1\u201017.7) respectively (<jats:italic>P\u00a0&lt;\u00a0<\/jats:italic>.05 for all). A nomogram based on these variables (histological parameters and immunohistochemical marker combinations) showed high reliability in both the training and validation cohorts (Harrell\u2019s C index: 0.701 and 0.716; 95% confidence intervals: 0.64\u20100.76 and 0.64\u20100.79 respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The combination of pSTAT3, pERK1\/2 and SYK immunoexpression with high lobular inflammatory activity and cirrhosis (fibrosis) predicts late HCC recurrence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14835","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T15:05:08Z","timestamp":1614438308000},"page":"1662-1674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pathological predictive factors for late recurrence of hepatocellular carcinoma in chronic liver disease"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-866X","authenticated-orcid":false,"given":"Ji Hae","family":"Nahm","sequence":"first","affiliation":[{"name":"Department of Pathology Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Biostatistics Collaboration Unit Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-9081","authenticated-orcid":false,"given":"Haeryoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology Seoul National University Hospital, Seoul National University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7346-5974","authenticated-orcid":false,"given":"Sun Young","family":"Yim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine Korea University School of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010hyun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pathology Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3629-4624","authenticated-orcid":false,"given":"Sang Hoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Sub","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Surgery Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5666-9753","authenticated-orcid":false,"given":"Ju\u2010Seog","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Systems Biology Division of Basic Science The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-7967","authenticated-orcid":false,"given":"Young Nyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology Yonsei University College of 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