High levels of histone H3 K27 acetylation and tri-methylation are associated with shorter survival in oral squamous cell carcinoma patients.

Abstract

Acetylation and trimethylation of histone H3 lysine 27 (H3K27ac and H3K27me3) generally activate and repress transcription, respectively. Concurrent activation of H3K27ac and H3K27me3 has been reported to correlate with poor prognosis in hepatocellular carcinoma. A high level of H3K27me3 has been shown to be associated with advanced oral squamous cell carcinoma (OSCC) tumour stage, but prognostic impact of H3K27ac level alone/or in combination with H3K27me3 in OSCC patients had not yet been reported. In this study, immunohistochemistry using specific antibodies against H3K27ac and H3K27me3 was performed on a series of 72 OSCC samples to investigate the association between H3K27ac and H3K27me3 levels and OSCC patient's survival. For each mark, the proportion of labelled cells (percentage) and the intensity of the labelling were measured, and a score of percentage x intensity was calculated. A high percentage of H3K27me3 positive cells was significantly associated with survival in univariate and multivariate analyses (logrank p-value < 0.05). Patients with high total scores of H3K27ac and H3K27me3 labelling also showed significantly shorter survival probabilities (logrank p-value < 0.05) compared to patients with low total scores of labelling for these histone posttranslational modifications (PTMs). Our findings suggest that the detection of both H3K27ac and H3k27me3 could help evaluating prognosis in OSCC patients.