A MicroRNA Expression Signature as Prognostic Marker for Oropharyngeal Squamous Cell Carcinoma
Menée à partir d'échantillons tumoraux prélevés sur 454 patients atteints d'un carcinome épidermoïde de l'oropharynx et menée à partir de données du projet "The Cancer Genome Atlas" portant sur 79 patients supplémentaires, cette étude identifie une signature, basée sur l'expression de 26 microARNs, permettant d'établir un pronostic
BACKGROUND : Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) may facilitate individualized patient management. This study was conducted to develop and validate a clinically feasible prognostic classifier based on microRNA sequencing (miRNA-seq) analysis.
METHODS : Tumor tissues were collected for miRNA-seq analysis from 324 OPSCC patients treated at Washington University in St. Louis and 130 OPSCC patients treated at Vanderbilt University, used for model training and validation, respectively. OPSCC patients (n = 79) from the TCGA were also included for independent validation. Univariate and multivariate Cox regression analyses were performed to identify miRNAs associated with disease outcomes.
RESULTS : A 26-miRNA signature was identified by miRNA-seq profiling analysis. Based on computed risk scores of the signature, we classified the patients into low- and high-risk groups. In the training cohort, the high-risk group had much shorter overall survival (OS) compared to the low-risk group [hazard ratio (HR) = 3.80, 95% CI = 2.37-6.10, P < .001]. Subgroup analysis further revealed that the signature was prognostic for HPV-positive OPSCCs (HR = 3.07, 95% CI = 1.65-5.71, P < .001). Multivariate analysis indicated that the signature was independent of common clinicopathologic factors for OPSCCs. Importantly, the miRNA signature was a statistically significant predictor of OS in independent validation cohorts (TCGA cohort: HR = 6.05, 95% CI = 2.10-17.37, P < .001; Vanderbilt cohort: HR = 7.98, 95% CI = 3.99-15.97, P < .001; Vanderbilt HPV-positive cohort: HR = 8.71, 95% CI = 2.70-28.14, P < .001).
CONCLUSION : The miRNA signature is a robust and independent prognostic tool for risk stratification of OPSCCs including HPV-positive OPSCCs.
Journal of the National Cancer Institute , résumé, 2019