Molecular description of ANGPT2 associated colorectal carcinoma

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, ANGPT2hi expression conferred a worst overall survival (HR = 1.20; p = 0.02). CRC stage, ANGPT2hi 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 ANGPT2hi 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. What's new? Angiopoietin‐2 (ANGPT2) is a prognostic factor in metastatic colorectal cancer (CRC). However, the molecular characterization of ANGPT2‐expressing CRC remains to be investigated. Here, using open source transcriptomic tools, the authors demonstrate that ANGT2‐expressing CRC is distributed across all Consortium Molecular Subtypes (CMS), and characterized by a poor prognosis and a specific gene expression pattern. ANGPT2 expression is not specifically related to a well‐defined molecular CRC entity. Beyond reflecting angiogenesis, genomic expression is associated with myeloid cell recruitment, invasion, stromal organization, and resistance to chemotherapy. A prognostic model was proposed using seric levels of ANGPT2, STC1, and CD138 in mCRC patients.