Prognostic impact of a novel gene expression profile classifier for the discrimination between metastatic and non-metastatic primary colorectal cancer tumors

Abstract

// María Laura Gutiérrez 1 , Luis Antonio Corchete 2 , María Eugenia Sarasquete 2 , María del Mar Abad 3 , Oscar Bengoechea 3 , Encarna Fermiñán 4 , María Fernanda Anduaga 5 , Sofía del Carmen 3 , Manuel Iglesias 5 , Carmen Esteban 5 , María Angoso 5 , Jose Antonio Alcazar 5 , Jacinto García 5, * , Alberto Orfao 1, * , Luis Muñoz-Bellvís 5, * and José María Sayagués 1, * 1 Cytometry Service-NUCLEUS, Cancer Research Center, IBMCC-CSIC/USAL, Department of Medicine, University of Salamanca, Institute of Biomedical Research of Salamanca, Biomedical Research Networking Centre Consortium-CIBER-CIBERONC, 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 Genomics Unit, Cancer Research Center, IBMCC-CSIC/USAL, Salamanca, Spain 5 Service of General and Gastrointestinal Surgery, Institute of Biomedical Research of Salamanca, Salamanca, Spain * These authors contributed equally to this work Correspondence to: Alberto Orfao, email: orfao@usal.es Keywords: sporadic colorectal cancer; metastatic; non-metastatic; primary tumor; gene expression profile Received: August 30, 2017      Accepted: October 28, 2017      Published: November 21, 2017 ABSTRACT Despite significant advances have been achieved in the genetic characterization of sporadic colorectal cancer (sCRC), the precise genetic events leading to the development of distant metastasis remain poorly understood. Thus, accurate prediction of metastatic disease in newly-diagnosed sCRC patients remains a challenge. Here, we evaluated the specific genes and molecular pathways associated with the invasive potential of colorectal tumor cells, through the assessment of the gene expression profile (GEP) of coding and non-coding genes in metastatic (MTX) vs. non-metastatic (non-MTX) primary sCRC tumors followed for >5 years. Overall, MTX tumors showed up-regulation of genes associated with tumor progression and metastatic potential while non-MTX cases displayed GEP associated with higher cell proliferation, activation of DNA repair and anti-tumoral immune/inflammatory responses. Based on only 19 genes a specific GEP that classifies sCRC tumors into two MTX-like and non-MTX-like molecular subgroups was defined which shows an independent prognostic impact on patient overall survival, particularly when it is combined with the lymph node status at diagnosis. In summary, we show an association between the global GEP of primary sCRC cells and their metastatic potential and defined a GEP-based classifier that provides the basis for further prognostic stratification of sCRC patients who are at risk of distant metastases.