IDENTIFICATION OF PROTEIN-CODING AND NONCODING GENE EXPRESSION SIGNATURES CORRELATED WITH MALIGNANT TRANSFORMATION AND METASTASES IN PANCREATIC CANCER

Abstract

Aim: To investigate possible roles of noncoding RNAs in Pancreatic Adenocarcinoma (PA), and to identify candidate marker genes for early diagnosis, prognosis and treatment management. Introduction: Early detection and targeted therapy are decisive for management of PA. Several lines of evidence indicate that ncRNAs may participate in mechanisms of regulation of gene expression in normal and cancer cells. Methods: A custom spotted cDNA 3,355-element microarray enriched in ncRNA probes was used to obtain expression profiles from 38 clinical samples; PA n = 15, normal adjacent pancreatic tissue (NAPT) n = 9, chronic pancreatitis (CP) n = 8, and 6 metastases (M). Among the probes in the array, 1,079 map to intronic or intergenic ncRNAs and 2,276 are exons from protein-coding genes. Results: Statistical analysis by SAM identified 323 transcripts (204 exonic, 89 intronic and 30 intergenic) that separate the samples according to histological type. We identified a signature of 24 transcripts (19 exonic, 3 intronic, and 2 intergenic; FDR<5%) that differentiate PA from PC and NAPT eliciting for malignant markers without inflammatory influence. We also identified 361 transcripts (213 exonic, 109 intronic, and 39 inter-genic; FDR<5%) as differentially expressed between PA and M, suggesting that those transcripts are associated with invasive phenotype. Conclusion: Our findings demonstrate the ubiquitous expression of intronic ncRNA in pancreatic cancer tissues, suggesting the involvement of this class of transcripts with malignant transformation and severity. Clinically, the characterization of these protein-coding transcripts and ncRNAs have the potential to contribute for new diagnostic molecular markers and putative therapeutic targets for treatment.