RNA sequencing analyses reveal novel differentially expressed genes and pathways in pancreatic cancer

Abstract

Gene expression microarrays have identified many tumor markers and therapeutic targets for pancreatic ductal adenocarcinoma (PDAC). However, microarray profilings have limited sensitivity and are prone to cross-hybridization between homologous DNA fragments. Here, we perform a transcriptome analysis of paired tumor and adjacent benign pancreatic tissues from 10 patients who underwent resection for PDAC. We identify a total of 2736 differentially expressed genes (DEGs) with false discovery rate less than 0.05, including 1554 upregulated, 1182 downregulated, and 6 microRNAs (miR-614, miR-217, miR-27b, miR-4451, miR-3609, and miR-612). Overexpression of five DEGs, i.e. KRT16, HOXA10, CDX1, SI, and SERPINB5 in tumors is confirmed by RT-PCR in 20 additional tissues. Overexpression of KRT16 in PDAC is also verified on protein level. In addition, top canonical pathways such as granulocyte adhesion and diapedesis pathway have been identified. Our study represents a comprehensive characterization of the PDAC transcriptome and provides insight to the mechanisms of pancreatic carcinogenesis and potential biomarkers and novel therapeutic targets for pancreatic cancer.