Analysis Of Genomic And Proteomic Expression Of Transforming Growth Factor β Regulator 4 In Clinico-Histopathologically Diagnosed Cases Of Oral Leukoplakia And Normal Healthy Mucosa – A Prospective Cross-Sectional Study

Oral squamous cell carcinoma (OSCC) is the commonest malignant neoplasm of the oral cavity affecting multiple sites in the oral cavity.1 As per reports of The World Health Organization (WHO), OSCC in South-East Asian countries accounts for nearly 40% of cases documented globally.2 India records second highest OSCC cases worldwide.3 OSCC is usually developed from lesions which are collectively referred to as OPMD (Oral Potentially Malignant Disorders).4  OPMD is a clinical diagnosis ; the histological diagnosis may be hyperplasia, hyperkeratosis, oral epithelial dysplasia (OED) or oral squamous cell carcinoma (OSCC) .OPMD includes leukoplakia, erythroplakia, oral submucous fibrosis, lichen planus etc. Among the various potential oral malignant lesions, leukoplakia is the commonest, having prevalence between 0.3 and 4.1% in general population, with Asia and Oceania reporting most cases.5,6 There are studies which attributes tobacco (smoking and smokeless) and intake of alcohol as risk factors common to both oral leukoplakia and squamous cell carcinoma (SCC).7Due to its common association of risk factor with OSCC, the malignant transformation rate of leukoplakia is significantly greater than other OPMDs. In literature, malignant transformation rate of leukoplakia varies from country to country ranging from less than 1 to 36% across various studies, depending upon factors like subtype of leukoplakia and patients’ characteristics.8   Recent studies on molecular pathophysiology in cases of oral leukoplakia have shown, resemblance to that of OSCC .These abnormalities reflect oncogenic potential of leukoplakia According to current result of molecular study of leukoplakia, it was noted that, TGF-β is one of the most important cytokines and had maximum sensitivity and specificity for differentiation of “SCC and dysplastic leukoplakia” from “non-dysplastic leukoplakia and normal mucosa” as well as for differentiation of OSCC from dysplastic leukoplakia.9

TGF-β is a member of the family of homologous polypeptides which is produced by platelets, endothelial cells, lymphocytes and macrophages. Transforming growth factor beta regulator 4 (TBRG4) is a regulator of TGF-β.10 TBRG4 is a human protein present on chromosome seven which is encoded by TBRG4 gene, also known as FAST kinase domain-containing protein 4 (FASTKD4)/cell cycle progression restoration protein 2 (CPR2).  Function of TBRG4 is to enable RNA binding activity. It also plays a role in mitochondrial mRNA processing, and its stability in mitochondrial matrix.11 TBRG4 has a novel regulatory role in progression in breast cancer and also plays a role in pathogenesis of several tumours like osteosarcoma, lung cancer and multiple myeloma etc.12Previous studies have suggested that TBRG4 might play a role in various lesions, including OSCC, by regulating epithelial cell differentiation and may affect the biological behaviour in the grading of epithelial dysplasia. Maximum patients are diagnosed at advanced stages of OSCC. Therefore, it is essentially   important to explore the molecular mechanisms involved in pathogenesis of cancer. Very few attempts have been made to establish the expression of TBRG4 in leukoplakia. Thus, our study aims to analyse the genomic and proteomic expression of TBRG4 in clinico-histopathologically diagnosed cases of oral leukoplakia