|
KMID : 1040620210270020313
|
|
Clinical and Molecular Hepatology
2021 Volume.27 No. 2 p.313 ~ p.328
|
|
|
Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognos- tic factor in hepatitis C virus-related hepatocellular carcinoma
|
|
Lin Ching-Chih
Liu Ta-Wei
Yeh Ming-Lun
Tsai Yi-Shan
Tsai Pei-Chien
Huang Chung-Feng
Huang Jee-Fu
Chuang Wan-Long
Dai Chia-Yen
Yu Ming-Lung
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Receptors, Somatotropin, Carcinoma, Hepatocellular, Hepacivirus, Recurrence, Prognosis
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
    
|
|