Upregulated histone deacetylase 2 gene correlates with the progression of oral squamous cell carcinoma

Article type: Research Article

Authors: Krishna, Akhilesh^a | Singh, Vineeta^b | Singh, Shraddha^{a; *} | Kumar, Sachil^c | Kumar, Vijay^d | Mehrotra, Divya^e | Singh, Uma Shankar^f | Mahdi, Abbas Ali^g

Affiliations: [a] Department of Physiology, King George’s Medical University, Lucknow, U.P, India | [b] Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, U.P, India | [c] Department of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh, Saudi Arabia | [d] Department of Surgical Oncology, King George’s Medical University, Lucknow, U.P, India | [e] Department of Oral and Maxillofacial Surgery, King George’s Medical University, Lucknow, U.P, India | [f] Department of Pathology, King George’s Medical University, Lucknow, U.P, India | [g] Department of Biochemistry, King George’s Medical University, Lucknow, U.P, India

Correspondence: [*] Corresponding author: Shraddha Singh, Department of Physiology, King George’s Medical University, Lucknow 226003, U.P, India. E-mail: [email protected].

Abstract: BACKGROUND: Histone deacetylases (HDACs) are considered as an essential regulator of cellular proliferation, differentiation, and apoptosis. The HDAC2 enzyme of Class I HDACs plays an important role in tumor progression of human malignancies. OBJECTIVE: The aim of the present study was to analyze the HDAC2 gene expression in pre-oral cancer and oral squamous cell carcinoma (OSCC), and its association with clinico-pathological features. METHODS: The HDAC2 protein expression was analyzed through the immunohistochemistry and western blot techniques in 82 oral pre-malignant, 90 OSCC, and 16 normal control tissues. qRT-PCR was used to quantify the mRNA fold change in all groups. RESULTS: The HDAC2 protein and mRNA levels were significantly higher in OSCC and pre-oral cancer groups compared to the controls. Immunostaining of HDAC2 protein was enhanced in 84.4% of OSCC and 67.1% of pre-cancerous tissue sections (p< 0.01). The mean protein level was analyzed as 1.96 ± 0.44 in oral carcinoma, 1.61 ± 0.39 in pre-cancer and 0.96 ± 0.10 in control tissues. In addition, HDAC2 mean protein level was associated with histological differentiation (OR = 25, p< 0.05) and tumor-node-metastasis (TNM) stages (OR = 6.2, p< 0.05) of OSCC patients. CONCLUSIONS: The upregulated HDAC2 gene in pre-cancer and OSCC tissues indicates its crucial role in the transformation of pre-malignant to malignant carcinoma. It could be a potential cancer biomarker of prognosis and targeted therapy in OSCC.

Keywords: Histone deacetylases, HDAC2 protein, OSCC, oral pre-cancer, oral cancer

DOI: 10.3233/CBM-190729

Journal: Cancer Biomarkers, vol. 29, no. 4, pp. 543-552, 2020