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Molecular description of ANGPT2 associated colorectal carcinoma
Author(s) -
Jary Marine,
Hasanova Reyhan,
Vienot Angélique,
Asgarov Kamal,
Loyon Romain,
Tirole Charline,
Bouard Adeline,
Orillard Emeline,
Klajer Elodie,
Kim Stefano,
Viot Julien,
Colle Elise,
Adotevi Olivier,
Bouché Olivier,
Lecomte Thierry,
Borg Christophe,
Feugeas Jean P.
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32993
Subject(s) - colorectal cancer , oncology , medicine , cancer research , transcriptome , stromal cell , gene expression , gene , bioinformatics , biology , cancer , genetics
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 four annotated platforms (GPL) and derived from localized CRC, ANGPT2 hi expression conferred a worst overall survival (HR = 1.20; p = 0.02). CRC stage, ANGPT2 hi expression but not Consortium Molecular Subtype (CMS) predict overall survival in multivariate analysis. ANGPT2 expression was not correlated with a specific CMS nor to RAS, RAF, MSI, p53, CIN, CIMP genomic alterations. Gene expression analysis revealed that ANGPT2 hi 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.