Journal Article

HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population

HARTMAN, MIKAEL, KHIN, LAY WAI, SALTO-TELLEZ, MANUEL, HOOI, SHING CHUAN, LU, GUO-DONG, IAU, PHILIP TSAU CHOONG, LEUNG, CAROL HO WING, YAP, CELESTIAL T, LER, SER YENG

2015

Overview

Histone deacetylases (HDACs) are enzymes involved in transcriptional repression. We aimed to examine the significance of HDAC1 and HDAC2 gene expression in the prediction of recurrence and survival in 156 patients with hepatocellular carcinoma (HCC) among a South East Asian population who underwent curative surgical resection in Singapore. We found that HDAC1 and HDAC2 were upregulated in the majority of HCC tissues. The presence of HDAC1 in tumor tissues was correlated with poor tumor differentiation. Notably, HDAC1 expression in adjacent non-tumor hepatic tissues was correlated with the presence of satellite nodules and multiple lesions, suggesting that HDAC1 upregulation within the field of HCC may contribute to tumor spread. Using competing risk regression analysis, we found that increased cancer-specific mortality was significantly associated with HDAC2 expression. Mortality was also increased with high HDAC1 expression. In the liver cancer cell lines, HEP3B, HEPG2, PLC5, and a colorectal cancer cell line, HCT116, the combined knockdown of HDAC1 and HDAC2 increased cell death and reduced cell proliferation as well as colony formation. In contrast, knockdown of either HDAC1 or HDAC2 alone had minimal effects on cell death and proliferation. Taken together, our study suggests that both HDAC1 and HDAC2 exert pro-survival effects in HCC cells, and the combination of isoform-specific HDAC inhibitors against both HDACs may be effective in targeting HCC to reduce mortality.

• Publisher: D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
• Subject: Adult / Aged / Antigens / Apoptosis / Biomarkers, Tumor - metabolism / Carcinoma, Hepatocellular - enzymology / Carcinoma, Hepatocellular - mortality / Cell Line, Tumor / Cell Proliferation / Colorectal cancer / Deoxyribonucleic acid / DNA / Enzymes / Female / Forecasts and trends / Gene expression / Gene Knockdown Techniques / Genetic aspects / Health aspects / hepatocellular carcinoma / Hepatoma / Histone Deacetylase 1 - metabolism / Histone Deacetylase 2 - metabolism / histone deacetylases / Humans / Hydrolases / Kinases / Liver cancer / Liver Neoplasms - enzymology / Liver Neoplasms - mortality / Male / Mammals / Middle Aged / Mortality / Polyclonal antibodies / Prognosis / Proportional Hazards Models / Regression Analysis / Risk Assessment / Singapore / Southeast Asian population / Tumors