Mitochondrial DNA content as a biomarker for oral carcinogenesis: correlation with clinicopathologic parameters.

Abstract

Background: Mitochondrial genome (mtDNA) exhibits greater vulnerability to mutations and/or copy number variations than nuclear counterpart (nDNA) in both normal and cancer cells due to oxidative stress generated by inflammation, viral infections, physical, mechanical, and chemical load. The study was designed to evaluate the mtDNA content in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). Various parameters were analyzed including its variation with human papillomavirus (HPV) during oral carcinogenesis.

Methods: The present cross-sectional study comprised of two hundred patients (100 OPMDs and 100 OSCCs) and 100 healthy controls. PCR amplifications were done for mtDNA content and HPV in OPMDs and OSCC using real-time and conventional PCR respectively.

Results: The relative mtDNA content was assessed quantitatively and it was observed that mtDNA was greater in OSCC (7.60±0.94) followed by OPMDs (5.93±0.92) and controls (5.37±0.95). It showed a positive linear correlation with habits and increasing histopathological grades. Total HPV-positive study groups showed higher mtDNA content (7.06±1.64) than HPV-negative counterparts (6.21±1.29).

Conclusions: An elevated mutant mtDNA may be attributed to increased free radicals and selective cell clonal proliferation in test groups. Moreover, sustained HPV infection enhances tumorigenesis through mitochondria mediated apoptosis. Since, mtDNA content is directly linked to oxidative DNA damage, these quantifications might serve as a surrogate measure for invasiveness in dysplastic lesions and typify their malignant potential.