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.

中文翻译：

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ANGPT2相关大肠癌的分子描述。

血管生成素-2（ANGPT2）是转移性结直肠癌（CRC）的预后因素。然而，尚需阐明哪些分子特征构成了与ANGPT2相关的预后不良的CRC子集。从Gene Expression Omnibus GEO和TCGA的TCGAbiolinks R-package收集了公共转录组数据集。经过适当的归一化处理后，使用Benjamini和Hochberg方法进行差异表达分析以了解错误的发现率。来自两项前瞻性临床试验的血浆用于研究ANGPT2相关生物标志物的临床影响。在来自本地CRC的四个注释平台（GPL）中包含的935个样本中，ANGPT2 ^hi表达赋予最差的总体生存率（HR = 1.20；p= 0.02）。在多变量分析中，CRC阶段，ANGPT2 ^hi表达而非联合体分子亚型（CMS）可以预测总体存活率。ANGPT2表达与特定的CMS，RAS，RAF，MSI，p53，CIN，CIMP基因组改变均无关。基因表达分析表明，ANGPT2 ^hi CRC亚群的特征是与血管生成相关的基因表达，髓样细胞的存在，基质组织和对化学疗法的抵抗力。提出了使用血清水平的ANGPT2，STC1和CD138检测97例mCRC患者的预后模型。我们的结果提供了证据，表明ANGPT2是局部CRC的预后因素，并定义了具有潜在临床应用意义的特定CRC亚组。