MicroRNA-based cancer mortality risk scoring system and hTERT expression linked with risk-adjusted treatment strategy in early-stage oral squamous cell carcinoma

We have developed and validated a novel microRNA (miRNA)-based prognostic model to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into ‘early-stage’ by the TNM system. A total of 836 early-stage 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 and low mortality risk categories. Within the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% (p<0.001) with surgery only. A Cox proportional hazard model on time-to-death suggests a hazard ratio of 0.37 when comparing surgery with neck dissection to surgery only (95% CI: 0.2-0.6; p=0.0005). For the low-risk group, surgery only without neck dissection was the most beneficial treatment modality, as opposed to the high-risk group, in which surgery with neck dissection significantly improved 5-year survival. Regardless of treatment selected, those with risk score ≥1 may benefit from additional therapy to prevent cancer relapse. Based on functional analysis of the prognostic miRNAs, we identified hTERT (human telomerase reverse transcriptase) as a promising drug target to prevent cancer relapse, thereby improving cancer-free survival. We also established a functional platform for patient-derived organoid-based drug testing in an effort to link prognostic marker-based mortality risk assessment with appropriate risk-adjusted therapy to improve overall survival.