Protein Kinase C Delta Is a Novel Biomarker for Hepatocellular Carcinoma

Backgrounds And Aims: Hepatocellular carcinoma (HCC) is the most common cancer with a poor prognosis. Identification of an alternative biomarker that can detect early-stage and conventional tumor marker-negative HCC is urgently needed. We found that protein kinase C delta (PKCδ) is specifically secreted from HCC cell lines into extracellular space and contributes to tumor development and that its serum levels were elevated in HCC patients. This study aimed to assess the practical usefulness of serum PKCδ for detecting HCC in chronic liver disease (CLD) patients.

Methods: Serum PKCδ levels in 313 CLD patients with and without HCC (n = 187 and 126, respectively) were measured using a sandwich enzyme-linked immunosorbent assay. The diagnostic performance of PKCδ for HCC was evaluated using the receiver operating characteristic curve analysis and was compared with that of conventional markers, α-fetoprotein (AFP), and des-γ-carboxy prothrombin (DCP).

Results: Serum PKCδ levels in HCC patients were significantly higher than those in CLD patients without HCC. PKCδ distinguished HCC patients from CLD patients without HCC, with high sensitivity and specificity. Subgroup analyses revealed that the diagnostic performance of PKCδ for HCC was comparable to that of AFP and DCP, and that approximately 40% of AFP/DCP double-negative HCC patients were positive for PKCδ. PKCδ yielded better diagnostic performance for detecting solitary small-sized (ie, very early stage) HCC than AFP and DCP. There was no significant correlation between serum PKCδ and AFP/DCP levels.

Conclusion: Serum PKCδ is a novel HCC biomarker, which is independent of and complementary to conventional markers. Specifically, PKCδ may be useful for detecting very early-stage or AFP/DCP double-negative HCC.