Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

Autor: Zhang Tong, Wang Yadi, He Dongning, Chen Shurui, Tong Qing, Chen Suxian
Rok vydání: 2019
Předmět:
Adult
lcsh:Diseases of the circulatory (Cardiovascular) system
Anthracycline
Heart Diseases
Bioinformatics
medicine.medical_treatment
Breast Neoplasms
030204 cardiovascular system & hematology
03 medical and health sciences
0302 clinical medicine
Breast cancer chemotherapy
Breast cancer
Risk Factors
microRNA
Gene expression
Databases
Genetic
Medicine
Humans
Anthracyclines
Gene Regulatory Networks
Circulating MicroRNA
Gene
030304 developmental biology
Aged
miRNA
0303 health sciences
Cardiotoxicity
Antibiotics
Antineoplastic
business.industry
Signaling pathway
Gene Expression Profiling
Computational Biology
Middle Aged
medicine.disease
body regions
MicroRNAs
lcsh:RC666-701
Cancer research
Biomarker (medicine)
Female
Cardiology and Cardiovascular Medicine
business
Signal Transduction
Research Article
Zdroj: BMC Cardiovascular Disorders
BMC Cardiovascular Disorders, Vol 20, Iss 1, Pp 1-10 (2020)
DOI: 10.21203/rs.2.16223/v2
Popis: Background The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. 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 results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-β signaling pathway and adhesion signaling pathway. 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.
Databáze: OpenAIRE
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