Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma.

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.

CONCLUSION:

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.

• Authors: Ching-Chih Lin, 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
• Journal: Clinical and molecular hepatology (Clin Mol Hepatol) Vol. 27 Issue 2 Pg. 313-328 (Apr 2021) ISSN: 2287-285X [Electronic] Korea (South)
• PMID: 33317258 (Publication Type: Journal Article)

Chemical References

• Receptors, Somatotropin

Topics

• Carcinoma, Hepatocellular (etiology)
• Down-Regulation
• Female
• Hepacivirus
• Hepatitis C (complications)
• Humans
• Liver Neoplasms (etiology)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Prognosis
• Receptors, Somatotropin