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

// Yixiang Mao 1, 2, 5 , Jianjun Shen 4 , Yue Lu 4 , Kevin Lin 4 , Huamin Wang 3 , Yanan Li 2 , Ping Chang 2 , Mary G. Walker 4 and Donghui Li 2 1 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215007, China 2 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 3 Department of Pathology and Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 4 Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA 5 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China Correspondence to: Donghui Li, email: dli@mdanderson.org Yixiang Mao, email: maoyix@suda.edu.cn Keywords: pancreatic cancer, RNA sequencing, transcriptome, pathway analysis Received: June 03, 2016     Accepted: February 27, 2017     Published: March 22, 2017 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.