Open Access

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

  • Authors:
    • Ser Yeng Ler
    • Carol Ho Wing Leung
    • Lay Wai Khin
    • Guo-Dong Lu
    • Manuel Salto-Tellez
    • Mikael Hartman
    • Philip Tsau Choong Iau
    • Celestial T. Yap
    • Shing Chuan Hooi
  • View Affiliations

  • Published online on: September 9, 2015     https://doi.org/10.3892/or.2015.4263
  • Pages: 2238-2250
  • Copyright: © Ler et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.
View Figures
View References

Related Articles

Journal Cover

November-2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ler SY, Leung CH, Khin LW, Lu G, Salto-Tellez M, Hartman M, Iau PT, Yap CT and Hooi SC: HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population. Oncol Rep 34: 2238-2250, 2015
APA
Ler, S.Y., Leung, C.H., Khin, L.W., Lu, G., Salto-Tellez, M., Hartman, M. ... Hooi, S.C. (2015). HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population. Oncology Reports, 34, 2238-2250. https://doi.org/10.3892/or.2015.4263
MLA
Ler, S. Y., Leung, C. H., Khin, L. W., Lu, G., Salto-Tellez, M., Hartman, M., Iau, P. T., Yap, C. T., Hooi, S. C."HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population". Oncology Reports 34.5 (2015): 2238-2250.
Chicago
Ler, S. Y., Leung, C. H., Khin, L. W., Lu, G., Salto-Tellez, M., Hartman, M., Iau, P. T., Yap, C. T., Hooi, S. C."HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population". Oncology Reports 34, no. 5 (2015): 2238-2250. https://doi.org/10.3892/or.2015.4263