Clinical Significance of Telomere Length and Associated Proteins in Oral Cancer

Abstract

Purpose: Telomere shortening is an important event during carcinogenesis. Although studies suggest role of multiple proteins in telomere length regulation, there is dearth of reports in oral cancer which is a leading malignancy in Asian countries especially in India. Thus the present study was carried out to study these mechanisms and explore the pathways involved in telomere—telomerase regulation and identify possible prognostic markers to understand the biology of oral tumors for better treatment approaches. Methods: Telomere length was determined by Southern Hybridisation method, telomeric repeat binding factor (TRF) 1 and 2 expression was detected by Western blot method and telomerase activation by telomeric repeat amplifi cation protocol. Statistical analysis was done using SPSS (Version 10) software. Results: Significant shortening of telomeres was seen in the tumor tissues as compared to normal tissues. Poor prognosis was observed in the patients with higher telomere length in malignant tissue, higher tumor to normal telomere length ratio (T/N TRF LR). Expression of TRF-2 but not TRF-1 protein was signifi cantly higher in the malignant tissues. We also observed telomerase activation in 75 malignant tissues.Conclusions: Our results reveal signifi cant clinical usefulness of telomere length, T/N TRF LR and telomerase activation in the prognosis of oral cancer patients. TRF-2 overexpression in malignant tissues appears to play an important role in telomere length shortening in oral cancer. Abbreviations: TRF—Terminal restriction fragment; TRF-1—telomeric repeat binding factor-1; TRF-2—telomeric repeat binding factor-2; T/N TRF LR—Tumor/ Normal TRF length ratio

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