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

Autor: Shing Chuan Hooi, Celestial T. Yap, Philip Iau, Carol Ho-Wing Leung, Ser Yeng Ler, Guo-Dong Lu, Mikael Hartman, Lay Wai Khin, Manuel Salto-Tellez
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Adult
Male
Cancer Research
Carcinoma
Hepatocellular
animal structures
Population
Histone Deacetylase 2
Apoptosis
Histone Deacetylase 1
Biology
Southeast asian
Bioinformatics
Risk Assessment
SDG 3 - Good Health and Well-being
Cell Line
Tumor
Southeast Asian population
medicine
Biomarkers
Tumor
Humans
education
Aged
Cell Proliferation
Proportional Hazards Models
Gene knockdown
education.field_of_study
Singapore
Oncogene
Liver Neoplasms
Cancer
General Medicine
Articles
hepatocellular carcinoma
Cell cycle
Middle Aged
medicine.disease
mortality
digestive system diseases
enzymes and coenzymes (carbohydrates)
Oncology
Hepatocellular carcinoma
Gene Knockdown Techniques
embryonic structures
Cancer research
Regression Analysis
Female
biological phenomena
cell phenomena
and immunity
Liver cancer
histone deacetylases
Zdroj: Ler, S Y, Leung, C H W, Khin, L W, Lu, G-D, Salto-Tellez, M, Hartman, M, Iau, P T C, Yap, C T & 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, vol. 34, no. 5, pp. 2238-2250 . https://doi.org/10.3892/or.2015.4263
Oncology Reports
DOI: 10.3892/or.2015.4263
Popis: 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.
Databáze: OpenAIRE
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