Prognostic implication of the loss of TGFBR2 expression in oral carcinoma.

Abstract

Oral squamous cell carcinoma (OSCC) is a disease that strikes many worldwide, accounting for more than 145,000 deaths annually. This study examined the role of Transforming Growth Factor Beta (TGFβ) signalling alterations in oral carcinogenesis and also its influence on the disease prognosis. In presented study, we evaluated the protein-level alterations of core TGFβ signalling members in 20 potentially malignant oral disorders (PMDs) - leukoplakia and submucous fibrosis and 87 oral cancer samples by western blotting. Further, we analysed the association between these alterations and prognosis of oral carcinoma. For statistical analyses, univariate test like Student's 't'-test to compare expression level of various genes and logrank test has been used to compare the Kaplan-Meier survival curves. The multivariate model such as Cox's proportional hazard regression was used to verify the independent influence of each variable on the survival endpoints. A gradual decrease in the expression of TGFβ signalling members like SMAD2, SMAD4, TGFBR1 and TGFBR2 have been noted from normal to PMD in oral cancers. The bio-activeforms, SMAD2/3 also showed a similar trend. SMAD3 protein was downregulated significantly in the PMD stage itself. Thus an inverse correlation was observed between expression of TGFβ members and oral cancer progression.Furthermore, oral cancer patients showing TGFBR2 downregulation exhibited poor disease-free survival (p=0.005) and poor overall survival (p=0.012).Thus, assessing the TGFBR2 protein levels can serve as one of the prognostic marker for oral cancer.