FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy.

OBJECTIVE: Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer, but not in normal tissues except for testis. This study aimed to investigate the expression and functional role of FMR1NB in glioma. METHODS: The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry, respectively, in glioma specimens from 83 patients at follow-up. The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines A172 and U251. RESULTS: FMR1NB mRNA and protein expression was detected in 58.8% (77/131) and 46.34% (57/123) of glioma tissues, respectively. FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome. Knockdown of FMR1NB induced apoptosis and suppressed proliferation, adhesion, migration, and invasion by modulating the expression of cyclin A, CDK2, caspase-3, E-cadherin, and N-cadherin in A172 and U251 cells. CONCLUSION: Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

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

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.