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, 622pg/mL) were significantly higher than peripheral HGF levels (564pg/mL) (P=0.026). The posthepatectomy portal HGF levels (699pg/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 >699pg/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 >699pg/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.