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Iranian Journal of Biotechnology، جلد ۲۲، شماره ۲، صفحات ۴۰-۵۱
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عنوان انگلیسی A meta-analysis of transcriptome data to investigate the effect of soy isoflavones on breast cancer cell
چکیده انگلیسی مقاله Background: Breast cancer ranks as the second highest cause of cancer-linked deaths in women, with varying rates 
between Western and Asian countries. The consumption of phytoestrogens can influence breast cancer occurrence.
Objective: To comprehend how soy isoflavones impact breast cancer cells, we conducted a meta-analysis, combining 
gene expression data from multiple studies. This approach aimed to identify crucial transcriptional characteristics driving 
breast cancer cell response to soy phytoestrogens.
Materials and Methods: The gene expression profiles obtained from the Gene Expression Omnibus and Array Express 
and were grouped into control and isoflavones exposure conditions. We performed a meta-analysis based on the effect 
size combination method to identify the differentially expressed genes (DEGs). In addition, we performed Gene Ontology 
(GO) enrichment analysis, pathway analysis, weighted gene co-expression network analysis (WGCNA) and recursive 
support vector machine (R-SVM) algorithm. 
Results: Based on this meta-analysis, we identified 3,890 DEGs, of which 2,173 were up-regulated and 1,717 were downregulated. For example, SGCG, PLK2, and TBC1D9 were the most highly down-regulated genes and EGR3, WISP2, 
and FKBP4 were the most highly expressed genes in the isoflavones exposure condition. The functional enrichment and 
pathway analysis were revealed “cell division” and “cell cycle” among the most enriched terms. Among the identified 
DEGs, 269 transcription factor (TF) genes belonged to 42 TF families, where the C2 H2 ZF, bZIP, and bHLH were the 
most prominent families. We also employed the R-SVM for detecting the most important genes to classify samples into 
isoflavones exposure and control conditions. It identified a subset of 100 DEGs related to regulation of cell growth, 
response to estradiol, and intermediate ribonucleoside monophosphate in the purine (IMP) metabolic process. Moreover, the WGCNA separated the DEGs into five discrete modules strongly enriched for genes involved in cell division, DNA 
replication, embryonic digit morphogenesis, and cell-cell adhesion.
Conclusion: Our analysis provides evidence suggesting that isoflavone affects various mechanisms in cells, including 
pathways associated with NF-κB, Akt, MAPK, Wnt, Notch, p53, and AR pathways, which can lead to the induction of 
apoptosis, the alteration of the cell cycle, the inhibition of angiogenesis, and interference in the redox state of cells. These findings can shed light on the molecular mechanisms that underlie the response of breast cancer cells to isoflavones.
کلیدواژه‌های انگلیسی مقاله breast cancer,Coexpression analysis,isoflavones,Meta-analysis,Microarray studies
نویسندگان مقاله Elham Ashrafi-Dehkordi |
Nutrition Research Center, Department of Food Hygiene and Quality Control, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

Ahmad Tahmasebi |
Nutrition Research Center, Department of Food Hygiene and Quality Control, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

Habil Zare |
Department of Computer Science, Texas State University, San Marcos, Texas, 78666, USA

Seyed Mohammad Mazloomi |
Nutrition Research Center, Department of Food Hygiene and Quality Control, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

نشانی اینترنتی https://www.ijbiotech.com/article_196865_e21ca233aae2fdec1a8c97567841c7fc.pdf
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