MicroRNABased Cancer Mortality Risk Scoring System and hTERT Expression in EarlyStage Oral Squamous Cell Carcinoma

Abstract

We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancerspecific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into "earlystage"by the TNM staging system. A total of 836 earlystage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the highrisk group, surgery with neck dissection significantly improved the 5year survival to 75% from 46% with surgery only (p<0.001); a Cox proportional hazard model on timetodeath demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2-0.6; p=0.0005). For the lowrisk group, surgery only was the treatment of choice associated with 5year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (p<0.0005). Overexpression of hTERT was also observed in the patientderived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERTexpressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these highrisk earlystage oral cancer patients.