{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:55:33Z","timestamp":1790445333570,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 103-2325-B-006-009, MOST 104-2325-B-006-001, MOST 105-2325-B-006-001 and MOST 106-2320-B-006-068-MY3"],"award-info":[{"award-number":["MOST 103-2325-B-006-009, MOST 104-2325-B-006-001, MOST 105-2325-B-006-001 and MOST 106-2320-B-006-068-MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-\u03b2) 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-\u03b2-induced EMT pathway.<\/jats:p>","DOI":"10.3390\/ijms22073782","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T10:34:12Z","timestamp":1617705252000},"page":"3782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway"],"prefix":"10.3390","volume":"22","author":[{"given":"Chih-Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Chi Mei Foundation Medical Center, Division of Neurosurgery, Department of Surgery, Tainan 710, Taiwan"},{"name":"Department 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, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Han","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Ho","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chin","family":"Hou","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tain-Junn","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department 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, Taiwan"},{"name":"Chi Mei Foundation Medical Center, Department of Neurology and Occupational Medicine, Tainan 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Tsung","family":"Chang","sequence":"additional","affiliation":[{"name":"Chi-Mei Foundation Medical Center, Departments of Pathology, Tainan 710, Taiwan"},{"name":"Chi-Mei Foundation Medical Center, Departments of Nursing, Tainan 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Chi-Mei Foundation Medical Center, Departments of Pathology, Tainan 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Ting","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ching","family":"Chio","sequence":"additional","affiliation":[{"name":"Chi Mei Foundation Medical Center, Division of Neurosurgery, Department of Surgery, Tainan 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Shen","family":"Shan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Division of General Surgery, Department of Surgery, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Chi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Tsan","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, 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