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Pathological predictive factors for late recurrence of hepatocellular carcinoma in chronic liver disease

 Ji Hae Nahm  ;  Hye Sun Lee  ;  Haeryoung Kim  ;  Sun Young Yim  ;  Ji-Hyun Shin  ;  Jeong Eun Yoo  ;  Sang Hoon Ahn  ;  Jin Sub Choi  ;  Ju-Seog Lee  ;  Young Nyun Park 
 LIVER INTERNATIONAL, Vol.41(7) : 1662-1674, 2021-07 
Journal Title
Issue Date
Carcinoma, Hepatocellular* / surgery ; Hepatectomy ; Humans ; Liver Neoplasms* / surgery ; Neoplasm Recurrence, Local ; Reproducibility of Results ; Retrospective Studies
chronic hepatitis ; cirrhosis ; hepatocellular carcinoma ; inflammation ; nomogram ; recurrence
Background & aims: 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 (>2 years after curative resection).

Methods: 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-periportal 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-tumourous liver tissues. Immunoexpression of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), plasminogen activator inhibitor-1, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) and spleen tyrosine kinase (SYK) was measured.

Results: 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 (1.2-3.3), 21.1 (4.3-102.7) and 6.0 (2.1-17.7) respectively (P < .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's C index: 0.701 and 0.716; 95% confidence intervals: 0.64-0.76 and 0.64-0.79 respectively).

Conclusions: The combination of pSTAT3, pERK1/2 and SYK immunoexpression with high lobular inflammatory activity and cirrhosis (fibrosis) predicts late HCC recurrence.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Nahm, Ji Hae(남지해) ORCID logo https://orcid.org/0000-0003-0902-866X
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Lee, Hye Sun(이혜선) ORCID logo https://orcid.org/0000-0001-6328-6948
Choi, Jin Sub(최진섭)
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