Khirade Mamata F, Lal Girdhari, Bapat Sharmila A
National Centre for Cell Science, NCCS Complex, Pune 411007, India.
Sci Rep. 2015 Aug 14;5:13248. doi: 10.1038/srep13248.
The hallmarks of cancer deem biological pathways and molecules to be conserved. This approach may be useful for deriving a prognostic gene signature. Weighted Gene Co-expression Network Analysis of gene expression datasets in eleven cancer types identified modules of highly correlated genes and interactive networks conserved across glioblastoma, breast, ovary, colon, rectal and lung cancers, from which a universal classifier for tumor stratification was extracted. Specific conserved gene modules were validated across different microarray platforms and datasets. Strikingly, preserved genes within these modules defined regulatory networks associated with immune regulation, cell differentiation, metastases, cell migration, metastases, oncogenic transformation, and resistance to apoptosis and senescence, with AIF1 and PRRX1 being suggested to be master regulators governing these biological processes. A universal classifier from these conserved networks enabled execution of common set of principles across different cancers that revealed distinct, differential correlation of biological functions with patient survival in a cancer-specific manner. Correlation analysis further identified a panel of 15 risk genes with potential prognostic value, termed as the GBOCRL-IIPr panel [(GBM-Breast-Ovary-Colon-Rectal-Lung)-Immune-Invasion-Prognosis], that surprisingly, were not amongst the master regulators or important network hubs. This panel may now be integrated in predicting patient outcomes in the six cancers.
癌症的特征表明生物途径和分子是保守的。这种方法可能有助于推导预后基因特征。对11种癌症类型的基因表达数据集进行加权基因共表达网络分析,确定了高度相关基因的模块以及在胶质母细胞瘤、乳腺癌、卵巢癌、结肠癌、直肠癌和肺癌中保守的交互网络,从中提取了用于肿瘤分层的通用分类器。特定的保守基因模块在不同的微阵列平台和数据集中得到了验证。引人注目的是,这些模块中的保守基因定义了与免疫调节、细胞分化、转移、细胞迁移、致癌转化以及对凋亡和衰老的抗性相关的调控网络,其中AIF1和PRRX1被认为是控制这些生物学过程的主要调节因子。来自这些保守网络的通用分类器能够在不同癌症中执行一组共同的原则,以癌症特异性方式揭示生物学功能与患者生存的独特、差异相关性。相关性分析进一步确定了一组具有潜在预后价值的15个风险基因,称为GBOCRL-IIPr组[(胶质母细胞瘤-乳腺癌-卵巢癌-结肠癌-直肠癌-肺癌)-免疫-侵袭-预后],令人惊讶的是,这些基因不在主要调节因子或重要网络枢纽之中。现在可以将该组基因整合到预测这六种癌症患者的预后中。