The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway
Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and eluc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3782 |
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| author | Chih-Wei Chen Cheng-Han Yang Yuan-Ho Lin Ya-Chin Hou Tain-Junn Cheng Sheng-Tsung Chang Yu-Hua Huang Shang-Ting Chung Chung-Ching Chio Yan-Shen Shan Hung-Chi Cheng Wen-Tsan Chang |
| author_facet | Chih-Wei Chen Cheng-Han Yang Yuan-Ho Lin Ya-Chin Hou Tain-Junn Cheng Sheng-Tsung Chang Yu-Hua Huang Shang-Ting Chung Chung-Ching Chio Yan-Shen Shan Hung-Chi Cheng Wen-Tsan Chang |
| author_sort | Chih-Wei Chen |
| collection | DOAJ |
| description | Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. Web-based open megadata minings revealed that FN was mainly mutated in the cBio Cancer Genomic Portal but dominantly overexpressed in the ONCOMINE (a cancer microarray database and integrated data-mining platform) in distinct tumor types. Furthermore, numerous different cancer patients with high FN indeed exhibited a poor prognosis in the PrognoScan mining, indicating that FN involves in tumor malignancy. To investigate further the significance of FN expression in glioma progression, tumor specimens from five malignant gliomas with recurrences that received at least two surgeries were enrolled and examined. The immunohistochemical staining showed that FN expression indeed determined the distinct progressions of malignant gliomas. Furthermore, the expression of vimentin (VIM), a mesenchymal protein that is strongly expressed in malignant cancers, was similar to the FN pattern. Moreover, the level of epithelial–mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-β) was almost recapitulated with the FN expression. Together, this study identifies a protein FN that can be used to diagnose GBM from low-grade astrocytoma; moreover, its expression functionally determines the malignant glioma progressions via TGF-β-induced EMT pathway. |
| first_indexed | 2024-03-10T12:34:52Z |
| format | Article |
| id | doaj.art-71a58af2e3c9444681762e3a8cb86a38 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:34:52Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-71a58af2e3c9444681762e3a8cb86a382023-11-21T14:22:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01227378210.3390/ijms22073782The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta PathwayChih-Wei Chen0Cheng-Han Yang1Yuan-Ho Lin2Ya-Chin Hou3Tain-Junn Cheng4Sheng-Tsung Chang5Yu-Hua Huang6Shang-Ting Chung7Chung-Ching Chio8Yan-Shen Shan9Hung-Chi Cheng10Wen-Tsan Chang11Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDepartment of Occupational Safety and Health/Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, Tainan 717, TaiwanChi-Mei Foundation Medical Center, Departments of Pathology, Tainan 710, TaiwanChi-Mei Foundation Medical Center, Departments of Pathology, Tainan 710, TaiwanDepartment of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanChi Mei Foundation Medical Center, Division of Neurosurgery, Department of Surgery, Tainan 710, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDue to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. Web-based open megadata minings revealed that FN was mainly mutated in the cBio Cancer Genomic Portal but dominantly overexpressed in the ONCOMINE (a cancer microarray database and integrated data-mining platform) in distinct tumor types. Furthermore, numerous different cancer patients with high FN indeed exhibited a poor prognosis in the PrognoScan mining, indicating that FN involves in tumor malignancy. To investigate further the significance of FN expression in glioma progression, tumor specimens from five malignant gliomas with recurrences that received at least two surgeries were enrolled and examined. The immunohistochemical staining showed that FN expression indeed determined the distinct progressions of malignant gliomas. Furthermore, the expression of vimentin (VIM), a mesenchymal protein that is strongly expressed in malignant cancers, was similar to the FN pattern. Moreover, the level of epithelial–mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-β) was almost recapitulated with the FN expression. Together, this study identifies a protein FN that can be used to diagnose GBM from low-grade astrocytoma; moreover, its expression functionally determines the malignant glioma progressions via TGF-β-induced EMT pathway.https://www.mdpi.com/1422-0067/22/7/3782gliomaglioblastoma multiforme (GBM)tumor recurrencetumor metastasisepithelial-mesenchymal transition (EMT)fibronectin (FN) |
| spellingShingle | Chih-Wei Chen Cheng-Han Yang Yuan-Ho Lin Ya-Chin Hou Tain-Junn Cheng Sheng-Tsung Chang Yu-Hua Huang Shang-Ting Chung Chung-Ching Chio Yan-Shen Shan Hung-Chi Cheng Wen-Tsan Chang The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway International Journal of Molecular Sciences glioma glioblastoma multiforme (GBM) tumor recurrence tumor metastasis epithelial-mesenchymal transition (EMT) fibronectin (FN) |
| title | The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway |
| title_full | The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway |
| title_fullStr | The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway |
| title_full_unstemmed | The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway |
| title_short | The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway |
| title_sort | fibronectin expression determines the distinct progressions of malignant gliomas via transforming growth factor beta pathway |
| topic | glioma glioblastoma multiforme (GBM) tumor recurrence tumor metastasis epithelial-mesenchymal transition (EMT) fibronectin (FN) |
| url | https://www.mdpi.com/1422-0067/22/7/3782 |
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