Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma
Multivariable analyses of global expression profiling are valid indicators of the prognosis of various diseases including brain cancers. To identify the candidates for markers of prognosis of glioblastoma, we performed multivariable analyses on the status of epithelial (EPI)−mesenchymal (M...
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MDPI AG
2019-10-01
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| author | Yasuo Takashima Atsushi Kawaguchi Ryuya Yamanaka |
| author_facet | Yasuo Takashima Atsushi Kawaguchi Ryuya Yamanaka |
| author_sort | Yasuo Takashima |
| collection | DOAJ |
| description | Multivariable analyses of global expression profiling are valid indicators of the prognosis of various diseases including brain cancers. To identify the candidates for markers of prognosis of glioblastoma, we performed multivariable analyses on the status of epithelial (EPI)−mesenchymal (MES) transition (EMT), glioma (GLI) stem cells (GSCs), molecular target therapy (MTT), and potential glioma biomarkers (PGBs) using the expression data and clinical information from patients. Random forest survival and Cox proportional hazards regression analyses indicated significant variable values for <i>DSG3</i>, <i>CLDN1</i>, <i>CDH11</i>, <i>FN1</i>, <i>HDAC3/7</i>, <i>PTEN</i>, <i>L1CAM</i>, <i>OLIG2</i>, <i>TIMP4</i>, <i>IGFBP2</i>, and <i>GFAP</i>. The analyses also comprised prognosis prediction formulae that could distinguish between the survival curves of the glioblastoma patients. In addition to the genes mentioned above, <i>HDAC1</i>, <i>FLT1</i>, <i>EGFR</i>, <i>MGMT</i>, <i>PGF</i>, <i>STAT3</i>, <i>SIRT1</i>, and <i>GADD45A</i> constituted complex genetic interaction networks. The calculated status scores obtained by principal component analysis indicated that GLI genes covered the status of EPI, GSC, and MTT-related genes. Moreover, survival tree analyses indicated that MES<sup>high</sup>, MES<sup>high</sup>GLI<sup>low</sup>, GSC<sup>high</sup>GLI<sup>low</sup>, MES<sup>high</sup>MTT<sup>low</sup>, and PGB<sup>high</sup> showed poor prognoses and MES<sup>middle</sup>, GSC<sup>low</sup>, and PGB<sup>low</sup> showed good prognoses, suggesting that enhanced EMT and GSC are associated with poor survival and that lower expression of EPI markers and the pre-stages of EMT are relatively less malignant in glioblastoma. These results demonstrate that the assessment of EMT and GSC enables the prediction of the prognosis of glioblastoma that would help develop novel therapeutics and de novo marker candidates for the prognoses of glioblastoma. |
| first_indexed | 2024-03-12T07:48:49Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:48:49Z |
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| spelling | doaj.art-15b6294168974b3997769ebbe581362b2023-09-02T20:45:04ZengMDPI AGCells2073-44092019-10-01811131210.3390/cells8111312cells8111312Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in GlioblastomaYasuo Takashima0Atsushi Kawaguchi1Ryuya Yamanaka2Laboratory of Molecular Target Therapy for Cancer, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanCenter for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga 849-8501, JapanLaboratory of Molecular Target Therapy for Cancer, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, JapanMultivariable analyses of global expression profiling are valid indicators of the prognosis of various diseases including brain cancers. To identify the candidates for markers of prognosis of glioblastoma, we performed multivariable analyses on the status of epithelial (EPI)−mesenchymal (MES) transition (EMT), glioma (GLI) stem cells (GSCs), molecular target therapy (MTT), and potential glioma biomarkers (PGBs) using the expression data and clinical information from patients. Random forest survival and Cox proportional hazards regression analyses indicated significant variable values for <i>DSG3</i>, <i>CLDN1</i>, <i>CDH11</i>, <i>FN1</i>, <i>HDAC3/7</i>, <i>PTEN</i>, <i>L1CAM</i>, <i>OLIG2</i>, <i>TIMP4</i>, <i>IGFBP2</i>, and <i>GFAP</i>. The analyses also comprised prognosis prediction formulae that could distinguish between the survival curves of the glioblastoma patients. In addition to the genes mentioned above, <i>HDAC1</i>, <i>FLT1</i>, <i>EGFR</i>, <i>MGMT</i>, <i>PGF</i>, <i>STAT3</i>, <i>SIRT1</i>, and <i>GADD45A</i> constituted complex genetic interaction networks. The calculated status scores obtained by principal component analysis indicated that GLI genes covered the status of EPI, GSC, and MTT-related genes. Moreover, survival tree analyses indicated that MES<sup>high</sup>, MES<sup>high</sup>GLI<sup>low</sup>, GSC<sup>high</sup>GLI<sup>low</sup>, MES<sup>high</sup>MTT<sup>low</sup>, and PGB<sup>high</sup> showed poor prognoses and MES<sup>middle</sup>, GSC<sup>low</sup>, and PGB<sup>low</sup> showed good prognoses, suggesting that enhanced EMT and GSC are associated with poor survival and that lower expression of EPI markers and the pre-stages of EMT are relatively less malignant in glioblastoma. These results demonstrate that the assessment of EMT and GSC enables the prediction of the prognosis of glioblastoma that would help develop novel therapeutics and de novo marker candidates for the prognoses of glioblastoma.https://www.mdpi.com/2073-4409/8/11/1312glioblastomaglioma stem cellepithelial-mesenchymal transitionmultivariable analysisprognosis prediction |
| spellingShingle | Yasuo Takashima Atsushi Kawaguchi Ryuya Yamanaka Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma Cells glioblastoma glioma stem cell epithelial-mesenchymal transition multivariable analysis prognosis prediction |
| title | Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma |
| title_full | Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma |
| title_fullStr | Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma |
| title_full_unstemmed | Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma |
| title_short | Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma |
| title_sort | promising prognosis marker candidates on the status of epithelial mesenchymal transition and glioma stem cells in glioblastoma |
| topic | glioblastoma glioma stem cell epithelial-mesenchymal transition multivariable analysis prognosis prediction |
| url | https://www.mdpi.com/2073-4409/8/11/1312 |
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