Pre-operative Plasma miR-21-5p Is a Sensitive Biomarker and Independent Prognostic Factor in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Resection

Abstract

Blood plasma microRNAs (miRNAs) are emerging as a clinically useful tool for non-invasive detection and prognosis estimation in various cancer types including pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to provide an independent validation of circulating miRNAs identified in previous studies as diagnostic and/or prognostic biomarkers in PDAC. Based on the literature search, 6 miRNAs were chosen as candidates for independent validation; miR-21-5p, miR-375, miR-155, miR-17-5p, miR-126-5p and miR-1290. Validation of these miRNAs was performed in a cohort of 25 patients with PDAC undergoing surgical resection and 24 healthy donors. Plasma levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of all tested miRNA in blood plasma of PDAC patients in comparison to healthy controls with miR-21-5p showing the highest analytical performance (p<0.001; AUC>0.99). Increased levels of miR-21-5p (p=0.045) and miR-375 (p=0.013) were significantly associated with overall survival. Multivariate analysis demonstrated that miR-21-5p is a significant unfavorable prognostic factor independent on other clinical variables including adjuvant chemotherapy (hazard ratio 2.95; 95% CI 1.06-8.18; p=0.038). Our preliminary data indicate promising diagnostic and prognostic utility of plasma miR-21-5p in PDAC patients.

Extracellular Vesicle-Dependent Cross-Talk in Cancer—Focus on Pancreatic Cancer

“…In addition, a high exosomal miR-21 expression was associated with poor OS in pancreatic cancer patients (median OS of 344 vs. 846 days for low expression) (78). These results are consistent with Karasek et al results which concluded that plasma levels of miR-21 were significantly higher in PDAC compared to healthy controls and associated with poor OS in PDAC (79).…”

Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma

“…Besides the tested EMT-regulating microRNAs, other microRNAs have been connected with great potential as biomarkers in PDAC as well. Among others, microRNAs -21, -155, -196a and -210 are shown to be potential non-invasive biomarkers for diagnosis, prognosis and/or therapy response [ 19 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Moreover, microRNA-21 antisense oligonucleotides are also linked with high potential in PDAC therapy as a partner for gemcitabine [ 74 ].…”

Prognostic and predictive factors in pancreatic cancer

“…In PDAC, both overexpression and downregulation of specific miRNAs have been associated with poor prognosis. Among others, higher levels of circulating miR-21, miR-155 and miR-221 correlated with outcomes [46][47][48][49]. Interestingly, the miRNA 200s family has been shown to suppressor tumor progression via EMT inhibition [50].…”