ANTISENSE INTRONIC NON-CODING RNA LEVELS IN PANCREATIC CANCER

Abstract

Pancreatic adenocarcinoma (PA) is one of the most aggressive and has the worst prognosis of all solid tumors. Despite overall improvements in diagnostic imaging and molecular techniques, it is difficult to diagnose PA in the earlier stages. Surgical resection remains the only hope for cure, although only 5% to 20% of patients are candidates at the time of presentation. Early detection and targeted therapy is very important for improving a patient"s chance of survival. Monitoring of differential gene expression is an important step towards a better understanding of molecular pathogenesis of PA. Several lines of evidence indicate that non-coding RNAs may participate in control mechanisms of regulation of gene expression in normal and cancer cells. The aim of this study was to analyse the transcriptional profile of intronic messages in PA, and to identify candidate marker genes for early diagnosis and for prognosis and treatment management. Methods: To investigate a possible role of intronic ncRNAs in PA, we used a spotted cDNA 3,355-element microarray enriched in ncRNA probes constructed in our laboratory. Among these probes, there are 820 mapping to introns of RefSeq genes and 259 sequences mapping to intergenic regions. We analysed a total of 41 patient pancreatic samples: PA n = 22, normal adjacent pancreatic tissue (NAPT) n = 13, and chronic pancreatitis (CP) n = 6. Results: In an analysis by t test, we agrouped the NAPT with PA and with CP, as we identified 92 genes (74 exonic, 10 intronic, and 5 inter-genic) altered in PA and 47 genes (27 exonic, 15 intronic, and 5 inter-genic) in CP, (P < 0.02). Conclusion: Our findings show that these gene expression signatures can distinguish PA from PC and revealed several candidate genes (in special, intronic genes) in this neoplasia for further characterization.