Identification and characterization of the gene expression profiles for protein coding and non-coding RNAs of pancreatic ductal adenocarcinomas

Abstract

// María Laura Gutiérrez 1 , Luis Corchete 2 , Cristina Teodosio 1 , María Eugenia Sarasquete 2 , María del Mar Abad 3 , Manuel Iglesias 4 , Carmen Esteban 4 , José María Sayagues 1,* , Alberto Orfao 1,* and Luis Muñoz-Bellvis 4,* 1 Cytometry Service-NUCLEUS, Department of Medicine, Cancer Research Center (IBMCC-CSIC/USAL) and IBSAL (University of Salamanca), Salamanca, Spain 2 Cancer Research Center and Service of Hematology (University Hospital of Salamanca), Salamanca, Spain 3 Department of Pathology (University Hospital of Salamanca), Salamanca, Spain 4 Service of General and Gastrointestinal Surgery and IBSAL (University Hospital of Salamanca), Salamanca, Spain * These authors have equally contributed to this study and they should both be considered as last author Correspondence to: Alberto Orfao, email: // Keywords : pancreatic ductal adenocarcinoma, gene expression profile, mRNA, non-coding RNA, EMT-like tumors Received : February 13, 2015 Accepted : May 13, 2015 Published : May 22, 2015 Abstract Significant advances have been achieved in recent years in the identification of the genetic and the molecular alterations of pancreatic ductal adenocarcinoma (PDAC). Despite this, at present the understanding of the precise mechanisms involved in the development and malignant transformation of PDAC remain relatively limited. Here, we evaluated for the first time, the molecular heterogeneity of PDAC tumors, through simultaneous assessment of the gene expression profile (GEP) for both coding and non-coding genes of tumor samples from 27 consecutive PDAC patients. Overall, we identified a common GEP for all PDAC tumors, characterized by an increased expression of genes involved in PDAC cell proliferation, local invasion and metastatic capacity, together with a significant alteration of the early steps of the cellular immune response. At the same time, we confirm and extend on previous observations about the genetic complexity of PDAC tumors as revealed by the demonstration of two clearly distinct and unique GEPs (e.g. epithelial-like vs . mesenchymal-like) reflecting the alteration of different signaling pathways involved in the oncogenesis and progression of these tumors. Our results also highlight the potential role of the immune system microenvironment in these tumors, with potential diagnostic and therapeutic implications.