Clinical value of nine circulating miRNAs in prognosis and diagnosis of PDAC

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas. Since early disease symptoms are undefined and specific biomarkers are lacking, about 80% of patients present with advanced, inoperable tumors that represent a daunting challenge. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. The miRNA has been emerged as promising cancer biomarkers for PDAC. Nowadays, have been identified several miRNAs in serum or plasma of PDAC patients. However, there are not many of common miRNAs between them, and not all the studies have compared the serum/ plasma expression with the corresponding miRNAs present in the pancreatic tumor tissue. Due to this and considering that PDAC is the seventh leading cause of cancer death in Mexico, we initially identified the miRNAs that are differentially expressed in tissue from PDAC patients residing in the Mexican Republic, to later find out which of these miRNAs are overexpressed in the serum of patients with this type of cancer. In this way, nine common miRNAs were identified in tissue and serum of PDAC patients, of which four of them (miRNAs 223-3p, miR 210-3p, miR100-5p and miR-221 3p) could be proposed as a signature for the diagnosis of PDAC with a sensitivity and specificity of 0.74 and 0.82 respectively for patients residing in the Mexican Republic. The 56 target mRNA of these 9 miRNAs were found to be mainly enriched in fatty acid oxidation, glucose homeostasis, amino acid transport organonitrogen compound catabolism. Finally, four of the target mRNA may serve as a prognostic marker for PDAC in tissue samples. Formalin-fixed and paraffin-embedded tissue (FFPE) from 25 PDAC surgical specimens and 13 non cancerous pancreatic tissue samples (5 blocks from post-mortem studies and 4 blocks of pancreas adjacent to the tumor) were included in our study. In order to isolate the total areas of the tumor and excluding stromal cells, tissue macrodissection was performed. For the microRNA differential expression analysis, the GeneChip microRNA 4.0 array (Thermo Fisher Scientific, Waltham, MA, USA) was used.