Expression and Prognostic Value Identification of Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) in Brain Low-Grade Glioma

Objective: This study aimed to reveal the potential function of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and emphasized its importance in brain low-grade glioma (LGG). Methods: We firstly explored the differential expression of MTHFD2 mRNA in LGG and normal tissues, followed by correlation analysis of MTHFD2 mRNA expression with patient's clinical characteristics. MTHFD2 protein expression in LGG and subcellular location were also evaluated. Then, survival analysis was performed to reveal the influence of MTHFD2 expression on the overall survival of patients, and Cox regression analysis was applied to predict the prognostic factor for overall survival of LGG. Finally, we performed functional analysis to reveal potential MTHFD2-associated pathways involved in LGG. Results: We found that MTHFD2 was highly expressed in LGG patients (P<0.05), and MTHFD2 expression was related to patient's age and IDH mutation status (all P<0.05). MTHFD2 protein was mainly localized to the mitochondria. Survival analysis showed that high expression of MTHFD2 desirably improved the prognosis of LGG patients (P<0.001), especially for those patients with age >= 45 years (P<0.05). But independent prognostic role of MTHFD2 in LGG was not observed. Pathway enrichment analysis indicated that MTHFD2 high expression significantly and positively participated in the pathway of one carbon pool by folate (all P<0.05). Conclusion: High expression of MTHFD2 was observed in LGG, which was favorable for the overall survival of LGG patients. Our results assumed that MTHFD2 high expression might play a pivotal role in LGG through positively regulating pathway of one carbon pool by folate.