Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray
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 diffe...
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| Format: | Article |
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MDPI AG
2019-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/7/282 |
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| author | Ali Mohamed Alshabi Basavaraj Vastrad Ibrahim Ahmed Shaikh Chanabasayya Vastrad |
| author_facet | Ali Mohamed Alshabi Basavaraj Vastrad Ibrahim Ahmed Shaikh Chanabasayya Vastrad |
| author_sort | Ali Mohamed Alshabi |
| collection | DOAJ |
| description | 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 (<i>MCM2</i>, <i>TCF4</i>, <i>OLR1</i>, <i>HSPA5</i>, <i>MAP1LC3B</i>, <i>SQSTM1</i>, <i>NEU1</i>, <i>HIST1H1B</i>, <i>RAD51</i>, <i>RFC3</i>, <i>MCM10</i>, <i>ISG15</i>, <i>TNFRSF10B</i>, <i>GBP2</i>, <i>IGFBP5</i>, <i>SOD2</i>, <i>DHF</i> and <i>MT1H</i>), 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. |
| first_indexed | 2024-12-13T00:53:19Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-13T00:53:19Z |
| publishDate | 2019-07-01 |
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| spelling | doaj.art-1f46f6a89f1347149035d0b8260b06892022-12-22T00:04:52ZengMDPI AGBiomolecules2218-273X2019-07-019728210.3390/biom9070282biom9070282Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression MicroarrayAli Mohamed Alshabi0Basavaraj Vastrad1Ibrahim Ahmed Shaikh2Chanabasayya Vastrad3Department of Clinical Pharmacy, College of Pharmacy, Najran University, Najran 66237, Saudi ArabiaDepartment of Pharmaceutics, SET’S College of Pharmacy, Dharwad, Karnataka 580002, IndiaDepartment of Pharmacology, College of Pharmacy, Najran University, Najran 66237, Saudi ArabiaBiostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad, Karnataka 580001, IndiaBreast 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 (<i>MCM2</i>, <i>TCF4</i>, <i>OLR1</i>, <i>HSPA5</i>, <i>MAP1LC3B</i>, <i>SQSTM1</i>, <i>NEU1</i>, <i>HIST1H1B</i>, <i>RAD51</i>, <i>RFC3</i>, <i>MCM10</i>, <i>ISG15</i>, <i>TNFRSF10B</i>, <i>GBP2</i>, <i>IGFBP5</i>, <i>SOD2</i>, <i>DHF</i> and <i>MT1H</i>), 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.https://www.mdpi.com/2218-273X/9/7/282pathway enrichment analysisprotein-protein interaction networkmicroRNA |
| spellingShingle | Ali Mohamed Alshabi Basavaraj Vastrad Ibrahim Ahmed Shaikh Chanabasayya Vastrad Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray Biomolecules pathway enrichment analysis protein-protein interaction network microRNA |
| title | Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray |
| title_full | Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray |
| title_fullStr | Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray |
| title_full_unstemmed | Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray |
| title_short | Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray |
| title_sort | exploring the molecular mechanism of the drug treated breast cancer based on gene expression microarray |
| topic | pathway enrichment analysis protein-protein interaction network microRNA |
| url | https://www.mdpi.com/2218-273X/9/7/282 |
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