Stage-Specific Co-expression Network Analysis for Cancer Biomarker Discovery
Stage-Specific Co-expression Network Analysis for Cancer Biomarker Discovery
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DOI：
10.1109/bibm49941.2020.9313242
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
R. Tanvir;A. Mondal
中科院分区：
文献类型：
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作者：
R. Tanvir;A. Mondal
识别癌症不同阶段的保守基因网络模块可能会揭示癌症发生和进展背后的机制。这项工作是基于两个假设。假设1：在所有癌症阶段中保守的网络模块是与癌症发展或癌症从起始到阶段到阶段再到转移的进展的轨迹相关的潜在生物标志物。假设2：为了验证这一假设，我们对乳腺浸润癌（Breast Invasive Carcinoma，BRCA）的基因表达和临床资料进行了分析。基因表达数据分为五组-I期至IV期和正常组织样品。首先，生成四个阶段和正常样本的共表达网络。其次，使用加权基因共表达网络分析（WGCNA）发现来自每个阶段特异性网络的模块。第三，进行生存分析以识别具有统计学意义的模块。第四，进行模块保存分析以确定来自一个阶段的模块是否在其他癌症阶段以及正常阶段中保存。最后，对具有遗传学意义和保守性的模块进行基因本体和途径富集分析，本研究发现了几个乳腺癌的基因网络模块，它们在所有癌症阶段都保留下来，并且在总生存率方面具有重要意义，因此，它们可以被认为是潜在的癌症生物标志物，与癌症发展的轨迹有关。发现在不同阶段不保守的模块可以被认为是阶段特异性生物标志物。
Identification of conserved gene network modules in different stages of cancer may lead to uncovering mechanisms behind cancer initiation and progression. This work is based on two hypotheses. Hypothesis-l: the network modules conserved in all cancer stages are potential biomarkers related to the trajectory of cancer development or progression of cancer from initiation to stage-to-stage to metastasis. Hypothesis-2: The network modules from a stage, which are not conserved in other stages, can be considered as the stage-specific biomarkers for diagnosis.To test the hypotheses, gene expression and clinical data of Breast Invasive Carcinoma (BRCA) from The Cancer Genome Atlas (TCGA) were used for analysis. Gene expression data was divided into five groups- stage I to stage IV and normal tissue samples. First, the co-expression networks for each of the four stages and normal samples were generated. Second, the modules from each of the stage-specific networks were discovered using weighted gene co-expression network analysis (WGCNA). Third, survival analysis was performed to identify the prognostically significant modules. Fourth, module preservation analysis was performed to determine whether a module from one stage is preserved in other cancer stages as well as in normal stage. Finally, gene ontology and pathway enrichment analyses were performed for the prognostically significant and conserved modules.The present study discovered several gene-network modules for breast cancer preserved in all cancer stages and are significant in overall survival; hence, they can be considered potential biomarkers for cancers, related to the trajectory of cancer development. The modules that were found not to be conserved in different stages can be considered as stage-specific biomarkers.