Abstract
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.
Highlights
Glioblastoma multiforme (GBM) is a primary neuroepithelial cancer in the central nervous system (CNS)
The results revealed that the FN expression in brain and CNS tissues was mainly low in both protein and RNA levels (Figure 1A,B)
IHC staining of a total of 12 glioma specimens showed that only two malignant gliomas displayed a high level of FN expression, and the other 10 gliomas were not detected in FN expression (Figure 1C,D)
Summary
Glioblastoma multiforme (GBM) is a primary neuroepithelial cancer in the central nervous system (CNS). This cancer accounts for 12% to 15% of all intracranial tumors and about 50% of astrocytomas [1]. Patients with GBM have a poor prognosis of just 12–15 months following standard therapy, with only 3–5% of patients surviving up to five years after diagnosis [2,3]. The current GBM treatment includes maximal resection, followed by radiotherapy with concomitant and adjuvant Temozolomide (TMZ) chemotherapy [4]. Despite these aggressive therapeutic regimens, GBM’s poor prognosis is mainly due to its high propensity for tumor recurrence. The prognostic biomarkers about cancer outcomes (e.g., disease recurrence and progression, and overall survival) are important for the treatment and management of GBM patients
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