Network-based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer.

ABSTRACT

Pancreatic cancer is regarded as the most fatal and aggressive malignancy cancer due to its low 5-year survival rate and poor prognosis. The approaches of early diagnosis and treatment are limited, which makes it urgent to identify the complex mechanism of pancreatic oncogenesis. In this study, we used RNA-seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in paired tumor and normal pancreatic samples from ten patients. More than 1000 differentially expressed genes were identified, nearly half of which were also found to be differentially expressed in the majority of examined patients. Functional enrichment analysis revealed that these genes were significantly enriched in multicellular organismal and metabolic process, secretion, mineral transport, and intercellular communication. In addition, only 24 differentially expressed miRNAs were found, all of which have been reported to be associated with pancreatic cancer. Furthermore, an integrated miRNA-mRNA interaction network was generated using multiple resources. Based on the calculation of disease correlation scores developed here, several genes present in the largest connected subnetwork, such as albumin, ATPase H+ /K+ exchanging alpha polypeptide and carcinoembryonic antigen-related cell adhesion molecule 1, were considered as novel genes that play important roles in the development of pancreatic cancer. Overall, our data provide new insights into further understanding of key molecular mechanisms underlying pancreatic tumorigenesis.