Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognos- tic factor in hepatitis C virus-related hepatocellular carcinoma
- Author:
Ching-Chih LIN
1
;
Ta-Wei LIU
;
Ming-Lun YEH
;
Yi-Shan TSAI
;
Pei-Chien TSAI
;
Chung-Feng HUANG
;
Jee-Fu HUANG
;
Wan-Long CHUANG
;
Chia-Yen DAI
;
Ming-Lung YU
Author Information
- Publication Type:Original Article
- From:Clinical and Molecular Hepatology 2021;27(2):313-328
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background/Aims:Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC.
Methods:The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed.
Results:GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C.
Conclusions:Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.
