Tumor DNA-dependent protein kinase catalytic subunit expression is associated with hepatitis B surface antigen status and tumor progression in patients with hepatocellular carcinoma

Abstract

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which plays an important role in the DNA damage response, has been reported to be associated with tumor progression in various carcinomas. However, the clinical significance of DNA-PKcs in hepatocellular carcinoma (HCC) patients remains unclear. In the present study, we determined the tumor expression of DNA-PKcs in 104 resected HCC specimens by immunohistochemistry. The DNA-PKcs expression was scored as follows; 0, negative staining; 1, staining of nuclei at the tumor edge; 2, staining of the nuclei deep within the tumor and/or the tumor cytoplasm. The relationships between tumor expression of DNA-PKcs and the clinical characteristics and patient outcomes were investigated. Among the 104 HCCs, the distribution of staining for DNA-PKcs was as follows: 32 tumors were assigned a score of 0, 27 tumors were assigned a score of 1, and 45 tumors were assigned a score of 2. Statistical analyses revealed that tumor DNA-PKcs expression was significantly associated with the HBs antigen (HBsAg) status, presence/absence of portal vein invasion, size of the largest tumor nodule (<3.0 cm/>3.0, cm), and the serum alpha-fetoprotein level. Significant differences in the overall survival and recurrence-free survival were observed between patients showing (staining score 1 or 2) and not showing (staining score 0) tumor DNA-PKcs expression (P = 0.049 and P = 0.045, respectively). Our results suggest that tumor expression of DNA-PKcs is associated with tumor progression, HBsAg status and the postoperative outcomes in patients with HCC.