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Prognostic impact of a novel gene expression profile classifier for the discrimination between metastatic and non-metastatic primary colorectal can... - PubMed - NCBI

2017 Nov 21;8(64):107685-107700. doi: 10.18632/oncotarget.22591. eCollection 2017 Dec 8.

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

Gutiérrez ML1, Corchete LA2, Sarasquete ME2, Del Mar Abad M3, Bengoechea O3, Fermiñán E4, Anduaga MF5, Del Carmen S3, Iglesias M5, Esteban C5, Angoso M5, Alcazar JA5, García J#5, Orfao A#1, Muñoz-Bellvís L#5, Sayagués JM#1.

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Abstract

Despite significant advances have been achieved in the genetic characterization of sporadic colorectal cancer (sCRC), the precise geneticevents 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.