Predictive value of osteopontin for the prognosis of patients with hepatitis B virus related hepatocellular carcinoma after radical liver resection

Abstract

Objective To evaluate the expressions of osteopontin (OPN), P53 and vascular endothelial growth factor (VEGF) in the hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) tissues and the relation between the OPN expression and the short-term recurrence and prognosis of patients after radical liver resection(R0). Methods A total of 237 HBV-related HCC tissue specimens from patients who received R0 hepatectomy in the Department of Hepatobiliary Surgery, Affiliated Hospital of Medical College, Qingdao University from January 2003 to December 2008, were studied retrospectively. There were 204 males and 33 females with the age range from 15 to 82 years old and the median age of 54 years old. The informed consents of all patients were obtained and the ethical committee approval was received. Eighty-one para-carcinoma tissue specimens within 1 cm close to the tumor and 79 biopsy specimens of liver cirrhosis were collected as the control group. The positive expression rate of OPN, P53, VEGF were examined using tissue microarray and PV-6000 two-step methods of immunohistochemistry. The relations between the OPN expression and the HCC patients’ clinic pathological parameters, the P53 expression, as well as VEGF expression were compared by chi-square test. Survival analysis was carried out using Kaplan-Meier survival curve and Log-rank test. The risk factor analysis of tumor short-term recurrence and the prognosis analysis were carried out using Cox proportional hazard model. Results All patients were followed up for 1~102 months (the median time 43 months) . Short-term recurrence of HCC was observed in 55 patients after R0 hepatectomy with the intrahepatic recurrence rate 56%(31/55) and the extrahepatic metastasis rate 44%(24/55). Among 89 patients without short-term recurrence 80%(71/89)developed intrahepatic recurrence and 20%(18/89) developed extrahepatic metastasis. The positive expression rates of OPN in the HCC tissues, para-cacinoma tissues and liver cirrhosis tissues were 37%(88/237), 17%(14/81) and 14%(11/79) respectively. There were significant differences among the OPN positive expression rates in the HCC tissues, para-cacinoma tissues and liver cirrhosis tissues (χ2=12.44, 16.53; P<0.05) . The positive expression rate of OPN in the patients with short-term HCC recurrence was 51%(28/55), 35% (31/89) in the non-short-term HCC recurrence patients, and 31%(29/93) in the recurrence-free patients. The positive expression rate of OPN in the patients with short-term HCC recurrence was evidently higher, compared with that in the non-short-term HCC recurrence and recurrence-free patients( χ2=4.181, 5.679; P=0.041, 0.017) . The positive expression rate of P53 and VEGF in the HCC tissues were 26%(61/237), 77.2%(183/237) respectively. The positive expression rate of P53 and VEGF in the OPN positive tissues were both higher than that in the OPN negative tissues. There were significant differences (χ2=6.947, 4.14; P<0.05) . The median survival time in the positive OPN expression group was 49.6 months, which was shorter than that in the negative group(84.0 months)(χ2=5.916, P=0.015). There was significant difference for the survival rates between 2 groups. The positive expression of OPN is the independent risk factor for short-term recurrence and the prognosis in patients with HBV related HCC after the operation. Conclusions The positive expression rate of OPN is significantly higher in the HBV related HCC tissues. The expression of OPN shows relation with P53 and VEGF expression. The positive expression of OPN is the independent risk factor for short-term recurrence and the prognosis in patients with HBV related HCC after the operation. The positive expression of OPN indicates higher incidence of short-term recurrence and poorer prognosis. Key words: Carcinoma, hepatocellular; Osteopontin; Recurrence; Prognosis; Liver resection; P53; Vascular endothelial growth factor