Significance of serum hepatocyte growth factor levels in patients with hepatocellular carcinoma undergoing hepatic resection

Background: Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen and may stimulate the proliferation and invasiveness of human hepatocellular carcinoma (HCC) cells through the c-met receptor. This study evaluates the significance of serum HGF levels in patients undergoing HCC resection. Study design: The peripheral and portal sera and HCC and non-tumorous tissues of 40 HCC patients, with tumor TNM stage I (n = 12), II (n = 17), and III (n = 11) diseases, who underwent hepatic resection were prospectively collected. Serum HGF levels were determined by enzyme-linked immunosorbent assay. The c-met protein expressions were examined by immunohistochemistry. Median follow-up time was 69 months. Results: The prehepatectomy portal HGF levels (median, 622 pg/mL) were significantly higher than peripheral HGF levels (564 pg/mL) (P = 0.026). The posthepatectomy portal HGF levels (699 pg/mL) were significantly higher than prehepatectomy portal HGF levels (P < 0.001). C-met expression was detected in 87.5% HCC and in 85.0% non-tumorous liver tissues. By Cox multivariate analysis, posthepatectomy portal HGF level >699 pg/mL (P < 0.001), multiple tumors (P = 0.042), and TNM stages II (P = 0.019) and III (P = 0.009) were independent factors related with survival. Patients with a posthepatectomy portal HCG level >699 pg/mL and with a positive c-met expression in HCC tissue have the worst survival. Conclusions: In HCC patients, high peripheral and portal HGF serum levels related with poor prognosis after hepatic resection. Hepatocyte growth factor and c-met receptor can be targets of future HCC postoperative treatment.