Elevated Expression of Histone Demethylase PHF8 Associates with Adverse Prognosis in Patients of Laryngeal and Hypopharyngeal Squamous Cell Carcinoma

Abstract

Aim: Overexpression of histone demethylase PHF8 has been reported to function as an oncoprotein in many cancers; however, the implications of PHF8 involvement in laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remain unclear. This study aims to explore the expression of PHF8 and its clinical significance in LHSCC. Materials & methods: Western blotting and immunohistochemistry were performed to evaluate PHF8 protein expression in fresh and archived LHSCC samples. Global expressions of H3K27 and H3K9 methylation were analyzed in a cell line with PHF8 siRNA treatment. Results & conclusion: In our study, PHF8 was upregulated in fresh LHSCC tissues. Immunohistochemical staining revealed that the expression of PHF8 was positively associated with T classification, clinical stage, primary tumor position and tumor relapse. Survival analysis demonstrated that high PHF8 expression was significantly associated with shorter overall survival and disease-free survival. Moreover, PHF8 regulates the levels of H3K9me2 and H3K27me2 in LHSCC. Taken together, PHF8 might be a novel prognostic marker for this disease.

Keywords::

• epigenetic marker
• H3K9
• H3K27
• histone demethylation
• laryngeal and hypopharyngeal squamous cell carcinoma
• metastasis
• PHF8
• recurrence
• squamous cell carcinoma of the head and neck
• survival time

Acknowledgements

U Makendra (Emory University) and J Shi (School of Public Health, Central South University) are acknowledged for their suggestions.

Financial & competing interests disclosure

This study was funded by grants from the National High Technology Research and Development Program of China (the Chinese 863 Program, no. 2012AA02A201), the National Natural Science Foundation of China (no. 81202128, 81372906, 81372426, 81172558, 81472696 and 81272974), the Research Fund for the Doctoral Program of Higher Education of China (no. 20120162120049) and the Freedom Explore Program of Central South University (no. 2012QNZT099). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.