Expression and Prognostic Role of Glia Maturation Factor-γ in Gliomas

Abstract

BackgroundGlia maturation factor-γ (GMFG) regulates actin cytoskeletal organization and promotes the invasion of cancer cells. However, its expression pattern and molecular function in gliomas have not been clearly defined.MethodsIn this study, public datasets comprising 2,518 gliomas samples were used to explore GMFG expression and its correlation with malignancy in gliomas. Immunohistochemistry (IHC) staining was performed to determine the expression of GMFG in gliomas using an in-house cohort that contained 120 gliomas samples. Gene ontology enrichment analysis was conducted using the DAVID tool. The correlation between GMFG expression and immune cell infiltration was evaluated using TIMER, Tumor Immune Single-Cell Hub (TISCH) database, and IHC staining assays. The Kaplan–Meier analysis was performed to determine the prognostic role of GMFG and its association with temozolomide (TMZ) response in gliomas.ResultsThe GMFG expression was higher in gliomas compared with non-tumor brain tissues both in public datasets and in-house cohort. High expression of GMFG was significantly associated with WHO grade IV, IDH 1/2 wild-type, and mesenchymal (ME) subtypes. Bioinformatic prediction and IHC analysis revealed that GMFG expression obviously correlated with the macrophage marker CD163 in gliomas. Moreover, both lower grade glioma (LGG) and glioblastoma multiforme (GBM) patients with high GMFG expression had shorter overall survival than those with low GMFG expression. These results indicate that GMFG may be a therapeutic target for the treatment of such patients. Patients with low GMFG expression who received chemotherapy had a longer survival time than those with high GMFG expression. For patients who received ion radiotherapy (IR) only, the GMFG expression level had no effect on the overall survival neither in CGGA and TCGA datasets.ConclusionThe GMFG is a novel prognostic biomarker for patients with both LGG and GBM. Increased GMFG expression is associated with tumor-associated macrophages (TAMs) infiltration and with a bad response to TMZ treatment.

LncRNA NDUFA6-DT: A Comprehensive Analysis of a Potential LncRNA Biomarker and Its Regulatory Mechanisms in Gliomas

“…Co-expression analysis revealed that in LGG, NDUFA6-DT exhibits a positive correlation with PHLPP2 [41] and GRIA2 [42], known for inhibiting glioma progression. In contrast, it demonstrates a negative correlation with GMFG [43], S100A6, and S100A11 [44], all of which are associated with promoting glioma progression. Similarly, in GBM, NDUFA6-DT demonstrates a negative correlation with SUMF1 [45], CD109 [46], MUC11 [47], and MYBPH [48], which are all implicated in promoting glioma progression.…”

Identification of GMFG as a novel biomarker in IgA nephropathy based on comprehensive bioinformatics analysis

“…Glia maturation factor (GMFG), primarily synthesized in inflammatory cells, is now recognized as a novel member of the actin depolymerization factor/cofilin superfamily of proteins [ 40 ]. Research indicates that GMFG plays a pivotal role in regulating the chemotaxis of neutrophils, lymphocytes, and monocytes, making it an integral component of the body's inflammatory response [ 41 ].…”

“…For instance, it has been shown to inhibit the growth of lung cancer by activating the p53 signaling pathway [ 50 ]. In the case of LGG, which exhibit higher levels of GMFG expression, it has been associated with worse overall survival [ 40 ]. Furthermore, GMFG has been found to play a critical role in the metastasis of epithelial ovarian cancer and colorectal cancer [ 51 , 52 ].…”

BCL2A1 is associated with tumor-associated macrophages and unfavorable prognosis in human gliomas

“…TMZ is a first-line treatment for glioma, and the MGMT promoter methylation status is a factor that predicts therapeutic responses to TMZ. However, the accuracy of MGMT promoter methylation in predicting responses to TMZ is limited [ 32 ]. Our study found that glioma patients with high BCL2A1 expression had poor responses to TMZ treatment.…”