Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

乳腺癌患者外周血miRNA与蒽环类药物心脏毒性关系的生物信息学分析

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作者:Wang Yadi, Chen Shurui, Zhang Tong, Chen Suxian, Tong Qing, He Dongning

Background

The current diagnostic

Conclusions

Changes in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-β signaling pathway and adhesion signaling pathway.

Methods

Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. Result: The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification

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