Prognostic and clinicopathological value of melanoma-associated antigen D4 in patients with glioma

Abstract

The aim of the present study was to evaluate the clinical importance of melanoma-associated antigen D4 (MAGE-D4) expression in glioma, and to identify it as a valuable prognostic biomarker and therapeutic target. To achieve this, the expression of MAGE-D4 protein in 124 tumor tissues from patients with glioma was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC), and the associations between MAGE-D4expression and clinicopathological factors were evaluated. The survival analysis demonstrated the significant prognostic value of MAGE-D4 in glioma using follow-up data. RT-qPCR and IHC analysis confirmed that MAGE-D4 mRNA and protein expression levels were significantly increased in glioma tissues compared with those in normal brain tissues. The present study demonstrated that the percentage of glioma tissues with high expression of MAGE-D4 mRNA was 67.74%, and the percentage positive for MAGE-D4 protein expression was 78.23%. All patients with high MAGE-D4 expression in cancerous tissues experienced significantly reduced median overall survival (OS; 18.00 vs. 33.29 months; P<0.001) and recurrence-free survival (RFS; 12.7 vs. 28.3 months; P<0.001) times compared with those with low MAGE-D4 expression. In the patients with lower grade glioma [World Health Organization (WHO), I–II], similar results were obtained for the OS (26.11 vs. 57.85 months; P=0.013) and RFS (22.7 vs. 55.3 months; P=0.010) times; however, in patients with high-grade glioma (WHO, III–IV), there were no significant differences between high and low MAGE-D4 expression levels with regard to OS and RFS times (P>0.05). Multivariate analysis indicated that high MAGE-D4 protein expression was an important independent prognostic factor for patients with glioma (hazard ratio, 2.384; P=0.005), and was significantly associated with higher grade glioma (P<0.001). These results indicated that MAGE-D4 may be a potential biomarker for glioma and an important prognostic factor for patients with new or recurring glioma.

Downregulation of Brain Enriched Type 2 MAGEs Is Associated With Immune Infiltration and Poor Prognosis in Glioma

“…Further, this association was independent of IDH status and other clinically relevant variables. The association of MAGED4 overexpression with poor prognosis of glioma patients has been previously reported ( 46 ). In agreement to this, our analysis revealed that while MAGED1 , which is co-expressed with MAGED4 , was associated with poor prognosis in glioma, it did not emerge as an independent prognostic factor in multivariate analysis.…”

Expression and Prognostic Value of Melanoma-Associated Antigen D2 in Gliomas

“…qRT-PCR was conducted as previously reported [ 9 ]. TRIzol reagent (Thermo Fisher Scientific, Waltham, MA, USA, #15596026) was used to extract the total RNA from glioma tissues and normal brain specimens.…”

“…IHC was conducted in accordance with previous research [ 9 ]. The tissues are formalin-fixed for 24 h at room temperature before being paraffin-embedded, and then cut into 4 µm-thick slices.…”

“…The melanoma-associated antigen D2 (MAGED2) is a member of the melanoma-associated antigen family, which is consistent with type-I genes (MAGE-A, -B, and -C) and type-II genes (MAGE-D, -E, -F, -G, and -H) [ 8 ]. The overexpression of melanoma-associated antigens (MAGEs) is associated with a poor prognosis in glioma patients [ 9 , 10 , 11 ]. One study used a database to search for type-II genes and came to the conclusion that the expression of type-II genes is related to significant clinical and molecular characteristics in gliomas [ 12 ].…”

Expression, Function, and Prognostic Value of MAGE-D4 Protein in Esophageal Squamous Cell Carcinoma

“…In contrast, relatively little is known about the localization and expression of type II MAGE proteins. Studies on type II MAGE-D4 have reported that its expression in normal tissues is restricted to the brain and ovary; however, it is overexpressed in several human malignancies, including lung, liver, oral, kidney, breast, and colorectal cancers, glioma (12)(13)(14)(15)(16)(17)(18), and ESCC, as previously reported by us (19). MAGE-D4 is a prominent tumor-associated antigen and has been shown to contribute to the proliferation, migration, and invasion of breast cancer and oral squamous cell carcinoma cells (14,16).…”