Over-expression of HDAC8 down-regulate CDKN2A is associated with worse prognosis of esophageal squamous cell carcinoma.

Abstract

BackgroundThe epigenetic alteration has an impact on cancer cell cycle regulation. Expression of histone deacetylase 8 (HDAC8) ruled out the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and this is linked with the prognosis of Esophageal cancer (EC) patients.MethodsBy the immunohistochemical staining, we examined the expression status of HDAC8 and CDKN2A protein of 110 esophageal squamous cell carcinoma (ESCC) patients in the tissue microarray. The nuclear staining intensity was counted by immunoreactivity scoring ranging from 0 to 12 and grouped them into two; weak or non-expression and over-expression.ResultsThe median follow-up duration of our study was 71 months postoperatively. Up-regulation of HDAC8 expression and down-regulation of CDKN2A (p16) indicate decreased 5-year overall survival (OS) (P=0.003) and (P=0.001) respectively and progression-free survival (PFS) (P=0.005, P=0.001) respectively, which are statistically significant and determined by Kaplan-Meier estimates using log-rank test. Consequently, HDAC8 and CDKN2A act as an independent prognostic biomarker, for OS and PFS that analyzed by multivariate cox-regression analysis, HR 1.173 with 95% CI: 0.215–6.416 and P=0.003 and HR 1.217 with 95% CI: 0.224–6.600 and P=0.005 respectively. Spearman rank test establish the negative correlation between HDAC8 and CDKN2A.ConclusionsOver-expression of HDAC8 and weak or no expression of CDKN2A have a worse impact on EC patients and indicate poor survival and progression of the disease and act as a promising prognostic parameter.