Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data Analysis
Anti-<i>VEGF</i> therapy is considered to be a useful therapeutic approach in many tumors, but the low efficacy and drug resistance limit its therapeutic potential and promote tumor growth through alternative mechanisms. We reanalyzed the gene expression data of xenografts of tumors of b...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/3/403 |
| _version_ | 1797542045668081664 |
|---|---|
| author | Kesavan R. Arya Ramachandran P. Bharath Chand Chandran S. Abhinand Achuthsankar S. Nair Oommen V. Oommen Perumana R. Sudhakaran |
| author_facet | Kesavan R. Arya Ramachandran P. Bharath Chand Chandran S. Abhinand Achuthsankar S. Nair Oommen V. Oommen Perumana R. Sudhakaran |
| author_sort | Kesavan R. Arya |
| collection | DOAJ |
| description | Anti-<i>VEGF</i> therapy is considered to be a useful therapeutic approach in many tumors, but the low efficacy and drug resistance limit its therapeutic potential and promote tumor growth through alternative mechanisms. We reanalyzed the gene expression data of xenografts of tumors of bevacizumab-resistant glioblastoma multiforme (GBM) patients, using bioinformatics tools, to understand the molecular mechanisms of this resistance. An analysis of the gene set data from three generations of xenografts, identified as 646, 873 and 1220, differentially expressed genes (DEGs) in the first, fourth and ninth generations, respectively, of the anti-<i>VEGF</i>-resistant GBM cells. Gene Ontology (GO) and pathway enrichment analyses demonstrated that the DEGs were significantly enriched in biological processes such as angiogenesis, cell proliferation, cell migration, and apoptosis. The protein–protein interaction network and module analysis revealed 21 hub genes, which were enriched in cancer pathways, the cell cycle, the <i>HIF1</i> signaling pathway, and microRNAs in cancer. The <i>VEGF</i> pathway analysis revealed nine upregulated (<i>IL6</i>, <i>EGFR</i>, <i>VEGFA</i>, <i>SRC</i>, <i>CXCL8</i>, <i>PTGS2</i>, <i>IDH1</i>, <i>APP</i>, and <i>SQSTM1</i>) and five downregulated hub genes (<i>POLR2H</i>, <i>RPS3</i>, <i>UBA52</i>, <i>CCNB1</i>, and <i>UBE2C</i>) linked with several of the <i>VEGF</i> signaling pathway components. The survival analysis showed that three upregulated hub genes (<i>CXCL8</i>, <i>VEGFA</i>, and <i>IDH1</i>) were associated with poor survival. The results predict that these hub genes associated with the GBM resistance to bevacizumab may be potential therapeutic targets or can be biomarkers of the anti-<i>VEGF</i> resistance of GBM. |
| first_indexed | 2024-03-10T13:25:03Z |
| format | Article |
| id | doaj.art-5cce014ba4f540b1b46b752dc7361ac2 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T13:25:03Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5cce014ba4f540b1b46b752dc7361ac22023-11-21T09:42:57ZengMDPI AGBiomolecules2218-273X2021-03-0111340310.3390/biom11030403Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data AnalysisKesavan R. Arya0Ramachandran P. Bharath Chand1Chandran S. Abhinand2Achuthsankar S. Nair3Oommen V. Oommen4Perumana R. Sudhakaran5Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala 695581, IndiaDepartment of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala 695581, IndiaDepartment of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala 695581, IndiaDepartment of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala 695581, IndiaDepartment of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala 695581, IndiaDepartment of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala 695581, IndiaAnti-<i>VEGF</i> therapy is considered to be a useful therapeutic approach in many tumors, but the low efficacy and drug resistance limit its therapeutic potential and promote tumor growth through alternative mechanisms. We reanalyzed the gene expression data of xenografts of tumors of bevacizumab-resistant glioblastoma multiforme (GBM) patients, using bioinformatics tools, to understand the molecular mechanisms of this resistance. An analysis of the gene set data from three generations of xenografts, identified as 646, 873 and 1220, differentially expressed genes (DEGs) in the first, fourth and ninth generations, respectively, of the anti-<i>VEGF</i>-resistant GBM cells. Gene Ontology (GO) and pathway enrichment analyses demonstrated that the DEGs were significantly enriched in biological processes such as angiogenesis, cell proliferation, cell migration, and apoptosis. The protein–protein interaction network and module analysis revealed 21 hub genes, which were enriched in cancer pathways, the cell cycle, the <i>HIF1</i> signaling pathway, and microRNAs in cancer. The <i>VEGF</i> pathway analysis revealed nine upregulated (<i>IL6</i>, <i>EGFR</i>, <i>VEGFA</i>, <i>SRC</i>, <i>CXCL8</i>, <i>PTGS2</i>, <i>IDH1</i>, <i>APP</i>, and <i>SQSTM1</i>) and five downregulated hub genes (<i>POLR2H</i>, <i>RPS3</i>, <i>UBA52</i>, <i>CCNB1</i>, and <i>UBE2C</i>) linked with several of the <i>VEGF</i> signaling pathway components. The survival analysis showed that three upregulated hub genes (<i>CXCL8</i>, <i>VEGFA</i>, and <i>IDH1</i>) were associated with poor survival. The results predict that these hub genes associated with the GBM resistance to bevacizumab may be potential therapeutic targets or can be biomarkers of the anti-<i>VEGF</i> resistance of GBM.https://www.mdpi.com/2218-273X/11/3/403vascular endothelial growth factorglioblastomaangiogenesisanti-<i>VEGF</i> therapydrug resistancedifferentially expressed genes |
| spellingShingle | Kesavan R. Arya Ramachandran P. Bharath Chand Chandran S. Abhinand Achuthsankar S. Nair Oommen V. Oommen Perumana R. Sudhakaran Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data Analysis Biomolecules vascular endothelial growth factor glioblastoma angiogenesis anti-<i>VEGF</i> therapy drug resistance differentially expressed genes |
| title | Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data Analysis |
| title_full | Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data Analysis |
| title_fullStr | Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data Analysis |
| title_full_unstemmed | Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data Analysis |
| title_short | Identification of Hub Genes and Key Pathways Associated with Anti-<i>VEGF</i> Resistant Glioblastoma Using Gene Expression Data Analysis |
| title_sort | identification of hub genes and key pathways associated with anti i vegf i resistant glioblastoma using gene expression data analysis |
| topic | vascular endothelial growth factor glioblastoma angiogenesis anti-<i>VEGF</i> therapy drug resistance differentially expressed genes |
| url | https://www.mdpi.com/2218-273X/11/3/403 |
| work_keys_str_mv | AT kesavanrarya identificationofhubgenesandkeypathwaysassociatedwithantiivegfiresistantglioblastomausinggeneexpressiondataanalysis AT ramachandranpbharathchand identificationofhubgenesandkeypathwaysassociatedwithantiivegfiresistantglioblastomausinggeneexpressiondataanalysis AT chandransabhinand identificationofhubgenesandkeypathwaysassociatedwithantiivegfiresistantglioblastomausinggeneexpressiondataanalysis AT achuthsankarsnair identificationofhubgenesandkeypathwaysassociatedwithantiivegfiresistantglioblastomausinggeneexpressiondataanalysis AT oommenvoommen identificationofhubgenesandkeypathwaysassociatedwithantiivegfiresistantglioblastomausinggeneexpressiondataanalysis AT perumanarsudhakaran identificationofhubgenesandkeypathwaysassociatedwithantiivegfiresistantglioblastomausinggeneexpressiondataanalysis |