Elucidation of β-Catenin Cyclin D1 Pathway in Oral Squamous Cell Carcinoma

Abstract

Background: Oral cancer is sixth most common cancer in India with poor overall disease free survival. In last decade major changes in the cancer management has happened but no such advantage has been seen in the survival of oral cancer patients. One major reason for the poor survival of head and neck squamous cell carcinoma (HNSCC) is lack of good predictive and prognostic biomarkers. Different studies have shown that in cancer cells, cell-cycle regulatory protein expression is altered. Cyclin D1 is a key regulatory molecule in cell cycle regulation. Many of the molecular alterations that cause abnormal biologic behaviour of cancer cells are based on aberrations of cell cycle regulation. Studies have demonstrated that Cyclin D1, c-Myc and MMP7 were important target genes of WNT signaling pathway and overexpression of them was highly associated with accumulation of β-Catenin and mutational defects of the WNT signaling pathway in numerous tumor types. Aim: This study was planned to characterize the β-Catenin and Cyclin D1 transcript level expression pattern in oral squamous cell carcinoma (OSCC) samples. Materials and Methods: Expression patterns of β-Catenin and Cyclin D1 were studied in OSCC at the transcript and protein levels by using qRT-PCR and immunohistochemistry (IHC) respectively. χ2, t-tests and ANOVA were used for the statistical analyses. Results: β-Catenin and Cyclin D1 were significantly overexpressed in oral squamous cell carcinoma cases when compared to normal. Correlation regression analysis showed the expression of Cyclin D1 and β-Catenin at mRNA level were positively correlated. Further, in immunohistochemical analysis β-Catenin showed cytoplasmic staining rather than nuclear. Conclusion: It is concluded that β-Catenin and Cyclin D1 mRNA level analysis using Real-time PCR could serve as biomarkers in oral squamous cell carcinoma since their expression is consistently altered in majority of the oral squamous cell carcinoma samples.