The diagnostic and prognostic potential of the EGFR/MUC4/MMP9 axis in glioma patients.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 11 2022
18 11 2022
Historique:
received:
14
06
2022
accepted:
10
11
2022
entrez:
18
11
2022
pubmed:
19
11
2022
medline:
23
11
2022
Statut:
epublish
Résumé
Glioblastoma is the most aggressive form of brain cancer, presenting poor prognosis despite current advances in treatment. There is therefore an urgent need for novel biomarkers and therapeutic targets. Interactions between mucin 4 (MUC4) and the epidermal growth factor receptor (EGFR) are involved in carcinogenesis, and may lead to matrix metalloproteinase-9 (MMP9) overexpression, exacerbating cancer cell invasiveness. In this study, the role of MUC4, MMP9, and EGFR in the progression and clinical outcome of glioma patients was investigated. Immunohistochemistry (IHC) and immunofluorescence (IF) in fixed tissue samples of glioma patients were used to evaluate the expression and localization of EGFR, MMP9, and MUC4. Kaplan-Meier survival analysis was also performed to test the prognostic utility of the proteins for glioma patients. The protein levels were assessed with enzyme-linked immunosorbent assay (ELISA) in serum of glioma patients, to further investigate their potential as non-invasive serum biomarkers. We demonstrated that MUC4 and MMP9 are both significantly upregulated during glioma progression. Moreover, MUC4 is co-expressed with MMP9 and EGFR in the proliferative microvasculature of glioblastoma, suggesting a potential role for MUC4 in microvascular proliferation and angiogenesis. The combined high expression of MUC4/MMP9, and MUC4/MMP9/EGFR was associated with poor overall survival (OS). Finally, MMP9 mean protein level was significantly higher in the serum of glioblastoma compared with grade III glioma patients, whereas MUC4 mean protein level was minimally elevated in higher glioma grades (III and IV) compared with control. Our results suggest that MUC4, along with MMP9, might account for glioblastoma progression, representing potential therapeutic targets, and suggesting the 'MUC4/MMP9/EGFR axis' may play a vital role in glioblastoma diagnostics.
Identifiants
pubmed: 36400876
doi: 10.1038/s41598-022-24099-4
pii: 10.1038/s41598-022-24099-4
pmc: PMC9674618
doi:
Substances chimiques
Mucin-4
0
Matrix Metalloproteinase 9
EC 3.4.24.35
ErbB Receptors
EC 2.7.10.1
Biomarkers
0
EGFR protein, human
EC 2.7.10.1
MUC4 protein, human
0
MMP9 protein, human
EC 3.4.24.35
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19868Subventions
Organisme : Medical Research Council
ID : MR/N005872/1
Pays : United Kingdom
Informations de copyright
© 2022. Crown.
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