Associating transcriptional modules with colon cancer survival through weighted gene co-expression network analysis.
Associating transcriptional modules with colon cancer survival through weighted gene co-expression network analysis.
复制标题
DOI：
10.1186/s12864-017-3761-z
复制
发表时间：
2017-05-09
期刊：
影响因子：
4.4
通讯作者：
Zhou HH
中科院分区：
文献类型：
--
作者：
Liu R;Zhang W;Liu ZQ;Zhou HH
结肠癌是一种受复杂基因网络影响的异质性疾病。因此，应该阐明网络和CC之间的关系，以获得对肿瘤生物学的进一步了解。加权基因共表达网络分析是一种用于从mRNA表达中提取共表达基因网络的强大技术，该分析在一个包含461名患者的发现数据集中识别了11个共调控模块。在发现(HR = 0.59；95%CI = 0.42-0.81)和验证(HR = 0.51；95%CI = 0.25-1.05)数据集中，细胞周期过程中丰富的转录模块与CC患者的无复发生存率相关。中心基因着丝粒蛋白-A(CENPA)的预后潜力也被确认，该基因的上调与良好的生存相关。另一个细胞周期时相相关基因模块与KRAS突变CC亚型患者的生存相关。几个基因的下调，包括在这个共表达模块中发现的那些基因，如细胞周期蛋白依赖性激酶1(CDK1)，与较差的存活率有关。基于网络的方法可能有助于发现预测II期或III期CC患者子集预后的生物标记物，这些方法也可能有助于指导个性化治疗。本文的在线版本(doi：10.1186/s12864-0173761-z)包含补充材料，授权用户可以使用。
Colon cancer (CC) is a heterogeneous disease influenced by complex gene networks. As such, the relationship between networks and CC should be elucidated to obtain further insights into tumour biology. Weighted gene co-expression network analysis, a powerful technique used to extract co-expressed gene networks from mRNA expressions, was conducted to identify 11 co-regulated modules in a discovery dataset with 461 patients. A transcriptional module enriched in cell cycle processes was correlated with the recurrence-free survival of the CC patients in the discovery (HR = 0.59; 95% CI = 0.42–0.81) and validation (HR = 0.51; 95% CI = 0.25–1.05) datasets. The prognostic potential of the hub gene Centromere Protein-A (CENPA) was also identified and the upregulation of this gene was associated with good survival. Another cell cycle phase-related gene module was correlated with the survival of the patients with a KRAS mutation CC subtype. The downregulation of several genes, including those found in this co-expression module, such as cyclin-dependent kinase 1 (CDK1), was associated with poor survival. Network-based approaches may facilitate the discovery of biomarkers for the prognosis of a subset of patients with stage II or III CC, these approaches may also help direct personalised therapies. The online version of this article (doi:10.1186/s12864-017-3761-z) contains supplementary material, which is available to authorized users.