CircuThe insulin-like growth factor-1 and expression of its binding protein-3 in chronic hepatitis C and hepatocellular carcinoma

Abstract

The role of growth factors produced by the liver, including insulin-like growth factor-1 (IGF-1) and its main binding protein, IGF binding protein-3 (IGFBP-3), in hepatitis C virus (HCV)-associated carcinogenesis has only partially been recognized and there is not much data available on the local expression of IGF-1 and IGFBP-3 in chronic hepatitis C (CH-C). Therefore, the aim of the present study was to evaluate the IGF-1 and IGFBP-3 serum levels and tissue expression in liver biopsies of CH-C patients (n=37) and hepatocellular carcinoma (HCC) samples (n=61) as related to age- and gender-matched control serum samples (n=15) and healthy liver samples (n=10). Serum concentrations of IGF-1 (S-IGF-1) and IGFBP-3 (S-IGFBP-3) were measured by the ELISA method. Tissue expression of proteins was detected using ABC immunocytochemistry and evaluated applying a spatial visualization technique. Concentrations of S-IGF-1 and hepatic expression of IGF-1 (H-IGF-1) proved to be lower in CH-C compared to the controls. No significant differences were detected in the concentration of S-IGFBP-3 between the studied groups but the S-IGF-1/IGFBP-3 ratio in the CH-C group was significantly lower compared to the control. H-IGFBP-3 was higher in CH-C compared to those in the control and HCC. In HCC, lower expression of H-IGF-1 was detected compared to the control and a higher H-IGF-1/IGFBP-3 ratio compared to CH-C. A negative correlation was detected between S-IGF-1 and S-IGF-1/IGFBP-3 ratio, on the one hand, and age, grading and concentration of α-fetoprotein (AFP) on the other, while H-IGFBP-3 was negatively correlated with BMI in the CH-C group. In patients with CH-C, the H-IGF-1/IGFBP-3 ratio was higher compared to that of the S-IGF-1/IGFBP-3 ratio. The studies documented a disturbed H-IGF-1 and H-IGFBP-3 in CH-C, which may be of significance in carcinogenesis. Examination of serum concentration and tissue expression of the two proteins and, first of all, estimation of the IGF-1/IGFBP-3 ratio may provide additional (to the estimation of IGF-1 and AFP) non-invasive markers in HCV-related liver injury.