MicroRNA molecular profiles associated with diagnosis, clinicopathological criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma
Menée sur deux cohortes successives de 48 et 24 patients atteints d'un carcinome canalaire du pancréas, cette étude évalue l'intérêt de mesurer l'expression de divers micro-ARNs pour le diagnostic et le pronostic de la maladie
Purpose:MicroRNAs (miRNAs) have potential as diagnostic and prognostic biomarkers and as therapeutic targets in cancer. We sought to establish the relationship between miRNA expression and clinicopathological parameters, including prognosis, in pancreatic ductal adenocarcinoma (PDAC). Experimental Design:Global miRNA microarray expression profiling of prospectively collected fresh-frozen PDAC tissue was performed on an initial test cohort of 48 patients, who had undergone pancreaticoduodenectomy between 2003 and 2008 at a single institution. We evaluated association with tumor stage, lymph node status, site of recurrence in addition to overall survival using Cox-regression multivariate analysis. Validation of selected potentially prognostic miRNAs was performed in a separate cohort of 24 patients. Results:miRNA profiling identified expression signatures associated with PDAC, lymph node involvement, high tumor grade, and 20 microRNAs were associated with overall survival. In the initial cohort of 48 PDAC patients, high expression of miR-21 (Hazard ratio (HR): 3.22, 95% Confidence Interval (CI):1.21-8.58) and reduced expression of miR-34a (HR 0.15, 95%CI: 0.06-0.37) and miR-30d (HR:0.30, 95%CI:0.12-0.79) were associated with poor overall survival following resection independent of clinical covariates. In a further validation set of 24 patients miR-21 and miR-34a expression again significantly correlated with overall survival (P = 0.031 and P = 0.001). Conclusions:Expression patterns of microRNAs are significantly altered in PDAC. Aberrant expression of a number of miRNAs were independently associated with reduced survival including over-expression of miR-21 and under-expression of miR-34a.
Clinical Cancer Research , résumé, 2011