Dataset Information

Bioinformatics-based identification of miR-542-5p as a predictive biomarker in breast cancer therapy.

ABSTRACT: Tamoxifen is the first-line hormone therapy for estrogen receptor alpha positive (ER?+) breast cancer. However, about 40% of patients with ER??+?breast cancer who receive tamoxifen therapy eventually develop resistance resulting in a poor prognosis. The aim of this study was to mine available data sets in the Gene Expression Omnibus (GEO) database, including in vitro (cell lines) and in vivo (tissue samples), and to identify all miRNAs associated with tamoxifen resistance (TamR) in breast cancer. Secondly, this study aimed to predict the key gene regulatory networks of newly found TamR-related miRNAs and evaluate the potential role of the miRNAs and targets as potential prognosis biomarkers for breast cancer patients.Microarray data sets from two different studies were used from the GEO database: 1. GSE66607: miRNA of MCF-7 TamR cells; 2. GSE37405: TamR tissues. Differentially expressed microRNAs (miRNAs) were identified in both data sets and 5 differentially expressed miRNAs were found to overlap between the two data sets. Profiles of GSE37405 and data from the Kaplan-Meier Plotter Database (KMPD) along with Gene Expression Profiling Interactive Analysis (GEPIA) were used to reveal the relationship between these 5 miRNAs and overall survival. The results showed that has-miR-542-5p was the only miRNA associated with overall survival of ER??+?breast cancer patients who received adjuvant tamoxifen. Targets of has-miR-542-5p were predicted by miRanda and TargetScan, and the mRNA expression of the three 3 target gene, Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Beta (YWHAB), Lymphocyte Antigen 9 (LY9), and Secreted Frizzled Related Protein 1 (SFRP1) were associated with overall survival in 2 different databases. Copy-number alterations (CNAs) of SFRP1 confer survival disadvantage to breast cancer patients and alter the mRNA expression of SFRP1 in cBioPortal database.This study indicates that miRNA has-miR-542-5p is associated with TamR and can predict prognosis of breast cancer patients. Furthermore, has-miR-542-5p may be acting through a mechanism involving the target genes YWHAB, LY9, and SFRP1. Overall, has-miR-542-5p is a predictive biomarker and potential target for therapy of breast cancer patients.

SUBMITTER: Zhu QN

PROVIDER: S-EPMC5769523 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bioinformatics-based identification of miR-542-5p as a predictive biomarker in breast cancer therapy.

Zhu Qiong-Ni QN Renaud Helen H Guo Ying Y

Hereditas 20180115

<h4>Background</h4>Tamoxifen is the first-line hormone therapy for estrogen receptor alpha positive (ERα+) breast cancer. However, about 40% of patients with ERα + breast cancer who receive tamoxifen therapy eventually develop resistance resulting in a poor prognosis. The aim of this study was to mine available data sets in the Gene Expression Omnibus (GEO) database, including in vitro (cell lines) and in vivo (tissue samples), and to identify all miRNAs associated with tamoxifen resistance (Tam ...[more]

PMID: 29371858

Similar Datasets

Project description:PurposeBreast cancer (BC) is characterized by concealed onset, delayed diagnosis, and high fatality rates making it particularly dangerous to patients' health. The purpose of this study was to use comprehensive bioinformatics analysis and experimental verification to find a new biomarker for BC diagnosis.MethodsWe comprehensively analyzed microRNA (miRNA) and mRNA expression profiles from the Gene Expression Omnibus (GEO) and screened out differentially-expressed (DE) miRNAs and mRNAs. We used the miRNet website to predict potential DE-miRNA target genes. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID), we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on overlapping potential target genes and DE-mRNAs. The protein-protein interaction (PPI) network was then established. The miRNA-mRNA regulatory network was constructed using Cytoscape and the analysis results were visualized. We verified the expression of the most up-regulated DE-miRNA using reverse transcription and a quantitative polymerase chain reaction in BC tissue. The diagnostic value of the most up-regulated DE-miRNA was further explored across three levels: plasma-derived exosomes, cells, and cell exosomes.ResultsOur comprehensive bioinformatics analysis and experimental results showed that hsa-miR-21-5p was significantly up-regulated in BC tissue, cells, and exosomes. Our results also revealed that tumor-derived hsa-miR-21-5p could be packaged in exosomes and released into peripheral blood. Additionally, when evaluating the diagnostic value of plasma exosomal hsa-miR-21-5p, we found that it was significantly up-regulated in BC patients. Receiver operating characteristic (ROC) analysis also confirmed that hsa-miR-21-5p could effectively distinguish healthy people from BC patients. The sensitivity and specificity were 86.7% and 93.3%, respectively.ConclusionThis study's results showed that plasma exosomal hsa-miR-21-5p could be used as a biomarker for BC diagnosis.

Project description:Breast cancer (BC) is the most common cancer among women worldwide. However, there is insufficient research that focuses on the expression and molecular mechanisms of microRNA (miR)‑204‑5p in BC. In the current study, data were downloaded from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena databases. They were then used to undertake a meta‑analysis that leveraged the standard mean difference (SMD) and summarized receiver operating characteristic (sROC) to evaluate the expression of the precursor miR‑204 and mature miR‑204‑5p in BC. Additionally, an intersection of predicted genes, differentially expressed genes (DEGs) from the TCGA database and the GEO database were plotted to acquire desirable putative genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein‑protein interaction (PPI) network analyses were performed to assess the potential pathways and hub genes of miR‑204‑5p in BC. A decreased trend in precursor miR‑204 expression was detected in 1,077 BC tissue samples in comparison to 104 para‑carcinoma tissue samples in the TCGA database. Further, the expression of mature miR‑204‑5p was markedly downregulated in 756 BC tissue samples in comparison to 76 para‑carcinoma tissue samples in the UCSC Xena database. The outcome of the SMD from meta‑analysis also indicated that the expression of miR‑204‑5p was markedly reduced in 2,306 BC tissue samples in comparison to 367 para‑carcinoma tissue samples. Additionally, the ROC and sROC values indicated that miR‑204‑5p had a great discriminatory capacity for BC. In GO analysis, 'cell development', 'cell surface activity', and 'receptor agonist activity' were the most enriched terms; in KEGG analysis, 'endocytosis' was significantly enriched. Rac GTPase activating protein 1 (RACGAP1) was considered the hub gene in the PPI network. In conclusion, miR‑204‑5p may serve a suppressor role in the oncogenesis and advancement of BC, and miR‑204‑5p may have crucial functions in BC by targeting RACGAP1.

Dataset Information

Bioinformatics-based identification of miR-542-5p as a predictive biomarker in breast cancer therapy.

Publications

Bioinformatics-based identification of miR-542-5p as a predictive biomarker in breast cancer therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets