High expressions of histone methylation- and phosphorylation-related proteins are associated with prognosis of oral squamous cell carcinoma in male population of Taiwan

Abstract

Since 2008, oral squamous cell carcinoma (OSCC) has climbed to the fourth place in cancer mortality in the male population of Taiwan. Epigenetic regulations including DNA methylation and histone modification control gene expression and play important roles during cancer progression. Since the relationship between histone modification and prognosis of OSCC is inconclusive, we collected 215 formalin-fixed and paraffin-embedded tissues from male patients having OSCC and surveyed them by tissue microarray-based immunohistochemical staining. The association between five histone modification-related genes, clinicopathological parameters, and prognosis of OSCC was examined. From tissue microarray immunohistochemistry staining results, we found that the nuclear staining intensity of ARK2 (Aurora kinase B-a serine/threonine-protein kinase of H3S10) was associated with poor clinical outcomes (≤3-year survival, p = 0.005). The cytosolic staining intensity of the ARK2 protein was associated with tumor stage (p = 0.006) and tumor size (T) of TNM staging system (p = 0.026). Cytoplasmic staining intensity of G9a (H3K9 methyltransferase) was associated with histological grade of differentiation (p = 0.026). EZH2 (H3K27 methyltransferase) and SUV39H1 (H3K9 methyltransferase) overexpressions in nuclei were, respectively, associated with lymph node metastasis (N, p = 0.016) and stage (p = 0.009). Our result suggests that overexpressions of histone modification-related proteins-ARK2, G9a, EZH2, and SUV39H1 but not SUV39H2 are associated with prognosis of OSCC in the male population of Taiwan. These proteins, especially ARK2, may serve as effective prognostic factors and can also be used as biomarkers for predicting various clinical outcomes of OSCCs in the Taiwanese population.