Clin Mol Hepatol.
2021 Apr;27(2):313-328. 10.3350/cmh.2020.0247.
Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognos- tic factor in hepatitis C virus-related hepatocellular carcinoma
- Lin CC1,2
- Liu TW1,2
- Yeh ML1,3,4
- Tsai YS1
- Tsai PC1
- Huang CF1,3,4
- Huang JF1,3,4
- Chuang WL1,3,4
- Dai CY
1,3,4,5 - Yu ML1,3,4,5
- Affiliations
-
- 1Division of Hepatobiliary, Department of Internal Medicine, Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- 2Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
- 3School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- 4Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
- 5Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
- KMID: 2514773
- DOI: http://doi.org/10.3350/cmh.2020.0247
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.
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