Expression of Ku86 and Presence of Ku86 Antibody as Biomarkers of Hepatitis B Virus Related Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a common disease and the third leading cause of cancer-related deaths worldwide. Level of the 82-kDa ATP-dependent DNA helicase II (Ku86) increases in some tumors, but its clinical use as a marker for HCC is rare. To examine the relationship between increases in Ku86 and the development of hepatitis B virus (HBV)-related HCC to define the relationship between Ku86 and HCC. Expression of Ku86 in tumor tissue, para-tumor tissue, and normal tissue was examined by immunohistochemistry, and Ku86 antibody titers in patient serum collected pre- and post-operatively were measured by ELISA. Long-term survival of the patients was also monitored. Ku86 staining in tumors was much stronger than in para-tumor and normal tissues. The expression of Ku86 was related to the tumor size, TNM stage, and tumor differentiation but not to gender, age, Child-Pugh score, tumor number, or α-fetoprotein levels. The long-term survival of patients with low Ku86 expression was longer. Patients with HCC had higher pre-operative Ku86 antibody levels. After surgical intervention, Ku86 antibody levels in patients with HCC declined significantly. Survival analysis showed that double-positive patients had the lowest survival rate, double-negative patients had the highest. Receiver operating characteristic curve analysis showed no significant difference between the AFP and Ku86 antibody. Multivariate analysis showed that Ku86 protein and Ku86 antibodies were independent prognostic factors of overall survival. Ku86 and Ku86 antibodies are promising tumor markers for early detection and prognosis prediction of HBV-related HCC.