MicroRNA-based risk scoring system to identify early-stage oral squamous cell carcinoma patients at high-risk for cancer-specific mortality

Background: For early-stage oral squamous cell carcinoma (OSCC), there is no existing risk-stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer-specific mortality. Methods: A total of 568 early-stage OSCC patients who had surgery only and also with available 5-year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT-PCR. The final 5-plex prognostic marker panel was utilized to generate a cancer-specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts. Results: The risk score from the 5-plex marker panel consisting of miRNAs-127-3p, 4736, 655-3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low-risk group, the high-risk group had 23-fold increased mortality risk (hazard ratio 23, 95% confidence interval 13-42), with a median time-to-recurrence of 6 months and time-to-death of 11 months (vs >60 months for each among low-risk patient; p <.001). Conclusion: The miRNA-based 5-plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early-stage OSCC.