Expression of hepatoma‐derived growth factor in hepatocellular carcinoma

BACKGROUND Hepatoma‐derived growth factor (HDGF) is a novel growth factor derived from a hepatoma cell line. The current study was designed to elucidate the role of HDGF expression during the pathogenesis of hepatocellular carcinoma (HCC). METHODS HDGF expression in hepatoma cell lines was analyzed using the reverse transcriptase–polymerase chain reaction (RT‐PCR), Western blot analysis, and immunofluorescence analysis. Immunohistochemical studies were performed to examine the intensity and spatial distribution of HDGF immunostaining in 105 HCC specimens. To evaluate its prognostic value, the labeling index of HDGF immunostaining was analyzed for potential correlations with the clinicopathologic characteristics of HCC. RESULTS RT‐PCR and Western blot analysis detected increased HDGF expression in malignant hepatoma cell lines. In resected HCC specimens, HDGF immunostaining was detected in the nuclei and cytoplasm of hepatocytes and hepatoma cells. HDGF levels in hepatoma tissue samples were significantly higher than in adjacent nontumor tissue samples (P < 0.05). Elevated nuclear HDGF levels were found to be correlated with loss of differentiation features (P < 0.05), absence of tumor capsules (P < 0.01), high α‐fetoprotein levels (P < 0.05), and overexpression of proliferating cell nuclear antigen (P < 0.001). Kaplan–Meier analysis indicated that patients with higher nuclear HDGF levels had a shorter duration of survival and a higher incidence of recurrence (P < 0.001). Multivariate analysis indicated that for patients with HCC, the nuclear HDGF level is an independent prognostic factor for overall and disease‐free survival. CONCLUSIONS Increased HDGF expression is correlated with the proliferating states of HCC and represents a novel prognostic factor for patients with HCC who have undergone surgery. Cancer 2003;98:1444–56. © 2003 American Cancer Society. DOI 10.1002/cncr.11653 Hepatoma‐derived growth factor (HDGF) is a novel mitogen for hepatocytes. The mRNA and protein levels of HDGF are up‐regulated in malignant hepatoma cells. In clinical hepatocellular carcinoma (HCC) specimens, increased nuclear HDGF expression is correlated with dedifferentiation, high serum α‐fetoprotein levels, proliferating cell nuclear antigen overexpression, tumor recurrence, and poor prognosis of patients with HCC.