Abstract 4621: Downregulation of Protein Kinase D1 in hepatocellular carcinoma (HCC): Potential as a diagnostic/prognostic molecular marker

Abstract

OBJECTIVE: Protein Kinase D1 (PKD1) plays an important role in several cellular processes such as cell proliferation, oxidative stress signaling, adhesion and motility. PKD1 is of particular interest in diagnosis, prognosis and treatment of human diseases because of its enzymatic activity and susceptibility to successful therapeutic targeting. In our earlier study we have demonstrated suppression of PKD1 expression in advance stage prostrate cancer. This led us to analyze PKD1 expression patterns in various other cancer tissue samples. MATERIAL AND METHODS: Tissue microarrays containing various cancer samples with corresponding normal tissues were used to investigate the expression profile of PKD1 using immunohistochemistry (Biocare Medical, Concord, CA). Further studies on PKD1 expression profile in hepatocellular carcinoma (HCC) were carried out using tissue microarray (TMA) containing HCC samples (n=70) with normal tissues (n=4) and a HCC TMA with hepatitis B viral history (HBV) containing HCC samples (n=100) with normal tissues (n=4) (AccuMax Array). Immunostaining was graded by two independent pathologists. Intensity and extent of staining scores were multiplied to obtain the composite score (CS) of each sample. RESULT: Differential expression pattern of PKD1 was observed in brain, skin, lung, kidney, thyroid and ovarian cancer samples. Along with stomach and colon cancer, HCC samples showed a marked downregulation of PKD1 expression compared to their respective normal tissues. PKD1 expression profile was further evaluated in a large cohort of HCC samples. Overall, HCC samples showed a significant (p>0.05) downregulation (Mean CS=6.0) of PKD1 expression compared to normal liver samples (Mean CS=11.4). Among cancer samples, advanced stage samples showed a relatively lower PKD1 expression (Mean CS=5.4) compared to early stage (Mean CS=6.6) HCC samples. Similarly, advance stage HCC samples with HBV showed a lower PKD1 expression (Mean CS=6.9) compared to early stage samples (Mean CS=9.6) and non neoplastic samples (Mean CS=12). CONCLUSION: The results of this study suggest suppression of PKD1 expression in HCC. In view of the limitations of the available diagnostic/prognostic studies for detection of HCC, the aberrant expression of PKD1 may serve as a novel biomarker for the diagnosis/prognosis of hepatocellular carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4621.