Identification of upstream transcription factors (TFs) for expression signature genes in breast cancer

Abstract

Breast cancer is a common malignancy among women with a rising incidence. Our intention was to detect transcription factors (TFs) for deeper understanding of the underlying mechanisms of breast cancer. Integrated analysis of gene expression datasets of breast cancer was performed. Then, functional annotation of differentially expressed genes (DEGs) was conducted, including Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, TFs were identified and a global transcriptional regulatory network was constructed. Seven publically available GEO datasets were obtained, and a set of 1196 DEGs were identified (460 up-regulated and 736 down-regulated). Functional annotation results showed that cell cycle was the most significantly enriched pathway, which was consistent with the fact that cell cycle is closely related to various tumors. Fifty-three differentially expressed TFs were identified, and the regulatory networks consisted of 817 TF-target interactions between 46 TFs and 602 DEGs in the context of breast cancer. Top 10 TFs covering the most downstream DEGs were SOX10, NFATC2, ZNF354C, ARID3A, BRCA1, FOXO3, GATA3, ZEB1, HOXA5 and EGR1. The transcriptional regulatory networks could enable a better understanding of regulatory mechanisms of breast cancer pathology and provide an opportunity for the development of potential therapy.

Chinese abstract

乳腺癌是一种常见的, 发病率逐年上升的女性恶性肿瘤。我们的目的是通过检测转录因子 (TFs), 以深入了解乳腺癌的发病机制。将乳腺癌基因表达谱进行综合分析后, 对筛查出的差异表达基因(DEGs)分别进行基因本体 (Gene ontology, GO) 功能富集度分析和京都基因和基因组百科全书(KEGG)通路功能分析。此外, 还确定了TFs并构建了全局转录调控网络。获得了7个可公开获得的GEO数据库, 差异表达基因结果显示1196个基因表达失调 (460个上调和736个下调) 。功能分析结果表明, 细胞周期是最为显著的富集途径, 这与细胞周期与各种肿瘤密切相关的事实一致。研究鉴定了53个差异表达的TF, 并且调节网包括了乳腺癌细胞中46个TFs和602个DEGs之间的基因位点与817个TF-靶位的相互作用。覆盖最下游DEGs顶部的10个TFs分别是SOX10, NFATC2, ZNF354C, ARID3A, BRCA1, FOXO3, GATA3, ZEB1, HOXA5和EGR1。转录调节网可以使人们更好地了解乳腺癌的病理调节机制, 并为乳腺癌的治疗提供潜在的治疗靶点。

Keywords:

• Breast cancer
• differentially expressed genes
• gene expression data
• transcription factor

Acknowledgements

The authors thank department of pathology and clinical laboratory of Yantaishan Hospital for providing pathological specimens of breast cancer.

Declaration of interest

The authors had no conflicts of interest to declare in relation to this article.

Supplementary material available online