Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray.

Basavarajvastrad BasavarajVastrad,Vastrad Vastrad,Alshabi Alshabi,Shaikh Shaikh

doi:10.3390/biom9070282

Basavarajvastrad BasavarajVastrad, Vastrad Vastrad + Show 2 more

Open Access

https://doi.org/10.3390/biom9070282

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Journal: Biomolecules	Publication Date: Jul 15, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: Najran University

Abstract

Breast cancer (BRCA) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers expressed during estradiol and tamoxifen treatment of BRCA. The microarray dataset of E-MTAB-4975 from Array Express database was downloaded, and the differential expressed genes (DEGs) between estradiol-treated BRCA sample and tamoxifen-treated BRCA sample were identified by limma package. The pathway and gene ontology (GO) enrichment analysis, construction of protein-protein interaction (PPI) network, module analysis, construction of target genes—miRNA interaction network and target genes-transcription factor (TF) interaction network were performed using bioinformatics tools. The expression, prognostic values, and mutation of hub genes were validated by SurvExpress database, cBioPortal, and human protein atlas (HPA) database. A total of 856 genes (421 up-regulated genes and 435 down-regulated genes) were identified in T47D (overexpressing Split Ends (SPEN) + estradiol) samples compared to T47D (overexpressing Split Ends (SPEN) + tamoxifen) samples. Pathway and GO enrichment analysis revealed that the DEGs were mainly enriched in response to lysine degradation II (pipecolate pathway), cholesterol biosynthesis pathway, cell cycle pathway, and response to cytokine pathway. DEGs (MCM2, TCF4, OLR1, HSPA5, MAP1LC3B, SQSTM1, NEU1, HIST1H1B, RAD51, RFC3, MCM10, ISG15, TNFRSF10B, GBP2, IGFBP5, SOD2, DHF and MT1H), which were significantly up- and down-regulated in estradiol and tamoxifen-treated BRCA samples, were selected as hub genes according to the results of protein-protein interaction (PPI) network, module analysis, target genes—miRNA interaction network and target genes-TF interaction network analysis. The SurvExpress database, cBioPortal, and Human Protein Atlas (HPA) database further confirmed that patients with higher expression levels of these hub genes experienced a shorter overall survival. A comprehensive bioinformatics analysis was performed, and potential therapeutic applications of estradiol and tamoxifen were predicted in BRCA samples. The data may unravel the future molecular mechanisms of BRCA.

Highlights

differential expressed genes (DEGs) (MCM2, TCF4, OLR1, HSPA5, MAP1LC3B, SQSTM1, NEU1, HIST1H1B, RAD51, RFC3, MCM10, ISG15, TNFRSF10B, GBP2, IGFBP5, SOD2, DHF and MT1H), which were significantly up- and down-regulated in estradiol and tamoxifen-treated Breast cancer (BRCA) samples, were selected as hub genes according to the results of protein-protein interaction (PPI) network, module analysis, target genes—miRNA interaction network and target genes-transcription factor (TF) interaction network analysis
The medians became consistent and were at an identical level following normalization (Figure 2B), suggesting that the normalization process is valid, and the normalized data may be used for additional analysis. Based on their BRCA status, samples were divided into six groups: T47D (n = 3), T47D (n = 3), T47D (n = 3), T47D (overexpressing Split Ends (SPEN) + estradiol)
By analyzing the pathway and Gene Ontology (GO) enrichment analysis, we found that DEGs were mainly enriched in the lysine degradation II, cholesterol biosynthesis, cell cycle, and response to cytokine, which provide a theoretical basis for studying the biological processes of BRCA

Summary

Introduction

BRCA accounts for 2,088,849 (11.6%)of new cancer cases [2] and 626,679 (6.6%) deaths in women worldwide, as per 2018 cancer statistics [3].Surgical resection is an effective treatment to advance patient. Biomolecules 2019, 9, 282 survival time [4], but it is only suitable for a small percentage of all cases [5].A number of other therapies, including radiotherapy [6], chemotherapy [7], hormone therapy [8], and immunotherapy [9], have been developed for BRCA treatment; there is limited information regarding the long-term survival rate, and the mortality rate of BRCA patients remains high [10]. Gene therapy and small molecule drugs are new strategies for cancer treatment, which have gained increasing consideration over the past few decades [11].

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