Molecular description of ANGPT2 associated colorectal carcinoma
Molecular description of ANGPT2 associated colorectal carcinoma
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DOI：
10.1002/ijc.32993
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发表时间：
2020-05-22
影响因子：
6.4
通讯作者：
Feugeas, Jean P.
中科院分区：
文献类型：
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作者：
Jary, Marine;Hasanova, Reyhan;Feugeas, Jean P.
血管生成素-2(ANGPT2)是转移性结直肠癌(CRC)的预后因素。然而，ANGPT2相关的预后不良的CRC亚群的分子特征仍有待阐明。公共转录数据集来自gene Expression Omnibus GEO和TCGAbiolinks R-Package for TCGA。经过适当的归一化处理后，采用Benjamini和Hochberg方法进行差异表达分析，以计算假发现率。来自两个前瞻性临床试验的血浆被用来研究ANGPT2相关生物标记物的临床影响。在来自4个注释平台(GPL)的935个样本中，ANGPT2(Hi)表达的总体生存率最差(HR=1.20；p=0.02)。在多因素分析中，CRC分期、ANGPT2(Hi)表达而不是联合体分子亚型(CMS)可以预测总的生存时间。ANGPT2的表达与特定的CMS无关，也与RAS、RAF、MSI、P53、CIN、CIMP的基因组改变无关。基因表达分析表明，ANGPT2(Hi)CRC亚群具有血管生成相关基因表达、髓系细胞存在、间质组织和化疗耐药等特点。用97例mCRC患者血清ANGPT2、STC1和CD138水平建立预后模型。我们的结果提供了证据，证明ANGPT2是局限性结直肠癌的预后因素，并定义了一个具有潜在临床应用的特定结直肠癌亚集。
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.