Molecular description of ANGPT2 associated colorectal carcinoma.

Fiche publication

Date publication

mars 2020

Journal

International journal of cancer

Auteurs

Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier , Pr BORG Christophe , Pr BOUCHE Olivier , Mme BOUARD Adeline , Dr VIENOT Angélique , Dr ASGAROV Kamal , Dr KIM Stephano , Pr FEUGEAS Jean-Paul , Dr LOYON Romain

Tous les auteurs :
Jary M, Hasanova R, Vienot A, Asgarov K, Loyon R, Tirole C, Bouard A, Orillard E, Klajer E, Kim S, Viot J, Colle E, Adotevi O, Bouché O, Lecomte T, Borg C, Feugeas JP

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32222972

Résumé

Angiopoietin-2 (ANGPT2) is a prognostic factor in metastatic colorectal cancer (CRC). Nevertheless, it remains to be elucidated which molecular characteristics make up the ANGPT2-related poor-prognosis CRC subset. Public transcriptomic datasets were collected from Gene Expression Omnibus GEO and with the TCGAbiolinks R-package for the TCGA. After appropriate normalization, differential expression analysis was performed using Benjamini and Hochberg method for false discovery rate. Plasma from two prospective clinical trials were used to investigate the clinical impact of ANGPT2-related biomarkers. In the 935 samples included in 4 annotated platforms (GPL) and derived from localized CRC, ANGPT2 expression conferred a worst overall survival (HR = 1.20; p = 0.02). CRC stage, ANGPT2 expression but not CMS (Consortium Molecular Subtype) predict overall survival in multivariate analysis. ANGPT2 expression was not correlated to a specific CMS nor to RAS, RAF, MSI, p53, CIN, CIMP genomic alterations. Gene expression analysis revealed that ANGPT2 CRC subset is characterized by angiogenesis-related gene expression, presence of myeloid cells, stromal organization and resistance to chemotherapy. A prognostic model was proposed using seric levels of ANGPT2, STC1 and CD138 in 97 mCRC patients. Our results provide evidence that ANGPT2 is a prognostic factor in localized CRC and defined a specific CRC subset with potential clinical implementation. This article is protected by copyright. All rights reserved.