Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis
Glioblastoma multiforme (GBM) is the most common infiltrating lethal tumor of the brain. Tumor heterogeneity and the precise characterization of GBM remain challenging, and the disease-specific and effective biomarkers are not available at present. To understand GBM heterogeneity and the disease pro...
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MDPI AG
2022-02-01
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| author | Dhanusha Yesudhas S. Akila Parvathy Dharshini Y-h. Taguchi M. Michael Gromiha |
| author_facet | Dhanusha Yesudhas S. Akila Parvathy Dharshini Y-h. Taguchi M. Michael Gromiha |
| author_sort | Dhanusha Yesudhas |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is the most common infiltrating lethal tumor of the brain. Tumor heterogeneity and the precise characterization of GBM remain challenging, and the disease-specific and effective biomarkers are not available at present. To understand GBM heterogeneity and the disease prognosis mechanism, we carried out a single-cell transcriptome data analysis of 3389 cells from four primary IDH-WT (isocitrate dehydrogenase wild type) glioblastoma patients and compared the characteristic features of the tumor and periphery cells. We observed that the marker gene expression profiles of different cell types and the copy number variations (CNVs) are heterogeneous in the GBM samples. Further, we have identified 94 differentially expressed genes (DEGs) between tumor and periphery cells. We constructed a tissue-specific co-expression network and protein–protein interaction network for the DEGs and identified several hub genes, including <i>CX3CR1, GAPDH, FN1, PDGFRA, HTRA1, ANXA2 THBS1, GFAP, PTN, TNC</i>, and <i>VIM</i>. The DEGs were significantly enriched with proliferation and migration pathways related to glioblastoma. Additionally, we were able to identify the differentiation state of microglia and changes in the transcriptome in the presence of glioblastoma that might support tumor growth. This study provides insights into GBM heterogeneity and suggests novel potential disease-specific biomarkers which could help to identify the therapeutic targets in GBM. |
| first_indexed | 2024-03-09T19:48:07Z |
| format | Article |
| id | doaj.art-3914776fb3a540e69bc26df51c2042f8 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T19:48:07Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-3914776fb3a540e69bc26df51c2042f82023-11-24T01:18:04ZengMDPI AGGenes2073-44252022-02-0113342810.3390/genes13030428Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data AnalysisDhanusha Yesudhas0S. Akila Parvathy Dharshini1Y-h. Taguchi2M. Michael Gromiha3Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, IndiaDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, IndiaDepartment of Physics, Chuo University, Bunkyo-ku, Tokyo 112-8551, JapanDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, IndiaGlioblastoma multiforme (GBM) is the most common infiltrating lethal tumor of the brain. Tumor heterogeneity and the precise characterization of GBM remain challenging, and the disease-specific and effective biomarkers are not available at present. To understand GBM heterogeneity and the disease prognosis mechanism, we carried out a single-cell transcriptome data analysis of 3389 cells from four primary IDH-WT (isocitrate dehydrogenase wild type) glioblastoma patients and compared the characteristic features of the tumor and periphery cells. We observed that the marker gene expression profiles of different cell types and the copy number variations (CNVs) are heterogeneous in the GBM samples. Further, we have identified 94 differentially expressed genes (DEGs) between tumor and periphery cells. We constructed a tissue-specific co-expression network and protein–protein interaction network for the DEGs and identified several hub genes, including <i>CX3CR1, GAPDH, FN1, PDGFRA, HTRA1, ANXA2 THBS1, GFAP, PTN, TNC</i>, and <i>VIM</i>. The DEGs were significantly enriched with proliferation and migration pathways related to glioblastoma. Additionally, we were able to identify the differentiation state of microglia and changes in the transcriptome in the presence of glioblastoma that might support tumor growth. This study provides insights into GBM heterogeneity and suggests novel potential disease-specific biomarkers which could help to identify the therapeutic targets in GBM.https://www.mdpi.com/2073-4425/13/3/428glioblastomatranscriptome analysistumor heterogeneitybiomarkersnetwork |
| spellingShingle | Dhanusha Yesudhas S. Akila Parvathy Dharshini Y-h. Taguchi M. Michael Gromiha Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis Genes glioblastoma transcriptome analysis tumor heterogeneity biomarkers network |
| title | Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis |
| title_full | Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis |
| title_fullStr | Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis |
| title_full_unstemmed | Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis |
| title_short | Tumor Heterogeneity and Molecular Characteristics of Glioblastoma Revealed by Single-Cell RNA-Seq Data Analysis |
| title_sort | tumor heterogeneity and molecular characteristics of glioblastoma revealed by single cell rna seq data analysis |
| topic | glioblastoma transcriptome analysis tumor heterogeneity biomarkers network |
| url | https://www.mdpi.com/2073-4425/13/3/428 |
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