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Significant down-regulation of GHR expression as a new unfavorable prognostic factor in HCV-related hepatocellular carcinoma revealed.

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), especially in 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 HCV-HCC patients.


Methods
The expression of GHR mRNA was investigated by quantitative real-time PCR (RT-qPCR) in paired tumor and adjacent non-tumorous (ANT) liver tissues of 200 HCV-HCC cases. 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 corresponding ANT. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age >60 years (p = 0.0111) and the worse clinicopathologic characteristics including AFP >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 poorer prognosis of HCC. Most importantly, the higher incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤ 0.1) was observed, indicating that lower expression levels of GHR had great risk for HCV-HCC progression.


Conclusion
Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in HCV-HCC.