Transforming growth factor‐α and epidermal growth factor receptor in chronic liver disease and hepatocellular carcinoma

Abstract

Aims/Background: Transforming growth factor‐α (TGF‐α) is a potent mitogen of normal and neoplastic hepatocytes. In addition, TGF‐α has been reported to play a pivotai role in hepatocarcinogenesis. To evaluate the significance of TGF‐α in chronic liver diseases and hepatocellular carcinoma, we examined serum TGF‐α, and expression of TGF‐α, epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) mRNA in liver tissues. Methods: Thirty‐five patients with chronic hepatitis (CH), 33 with liver cirrhosis (LC), 55 with hepatocellular carcinoma (HCC) and 53 normal controls (C) were enrolled in this study. Serum TGF‐α levels were measured by an enzyme‐linked immunosorbent assay. Expression of TGF‐α, EGFR, PCNA and β‐actin mRNA in liver tissues were examined by reverse transcription polymerase chain reaction. Results: Serum TGF‐α levels in C, CH, LC and HCC were 5.6 ± 2.1. 33.2 ± 8.3, 404.0 ± 173.0 and 100.3 ± 39.2 pg/ml, respectively. Serum TGF‐α level in LC was higher than in other diseases (p < 0.01, compared to CH, HCC and C, respectively). Serum TGF‐α levels exhibited a significant positive correlation with total bilirubin, ICGR15 and Pugh score (p < 0.01, p < 0.01 and p < 0.05, respectively), and increased in parallel with severity of disease according to Child classification. Although the ratios of TGF‐α, EGFR and PCNA mRNA to β‐actin mRNA were not significantly different among the diseases, the TGF‐α/β‐actin ratio correlated with EGFR/β‐actin and PCNA/β‐actin ratios (p < 0.001 and p < 0.0001, respectively), and EGFR/β‐actin ratio was related to PCNA/β‐actin ratio in ail patients, especially with HCC. Conclusion: The results of the present study suggest that serum TGF‐α levels are closely related to severity of liver dysfunction, and that hepatic expression of TGF‐α and EGFR correlates with proliferation of normal and neoplastic hepatocytes.