Exploring FAHD2B as a Potential Biomarker and Therapeutic Target in Gliomas

Introduction: About 80% of primary malignant brain tumors are gliomas, which are the most common and aggressive solid tumors of the central nervous system. They are characterized by rapid growth, abnormal angiogenesis, and widespread infiltration into surrounding tissues. Despite multimodal therapies, the prognosis remains poor, with a median survival of just 15 months. FAHD2B (Fumarylacetoacetate Hydrolase Domain Containing 2B) is a gene with hydrolase-like activity, known to be overexpressed in various malignant and non-cancerous conditions, though its role in gliomas is not yet understood. This pilot study aims to investigate the function of FAHD2B in gliomas, its clinicopathological significance, its role in tumor progression, and its potential as a prognostic marker.

Methods: In the present study, we assessed the potential roles of FAHD2B in the expression, prognostic value, and immune infiltration of glioma patients using different bioinformatics databases, such as TCGA dataset using UALCAN, protein atlas, Kaplan-Meier plot, and timer 2.0. We then validated FAHD2B expression in 10 glioma tissues and nodal tissue samples using quantitative reverse transcription PCR (RT-qPCR) and western blotting. We also conducted functional enrichment analysis using publicly available databases.

Results: FAHD2B mRNA and protein expression was significantly up-regulated in glioma patients compared to that in the normal tissues and pan cancer tissues. Up-regulated FAHD2B expression was associated with poor overall survival. Increased FAHD2B expression has also been linked to aggressive clinicopathological features, including advanced stage, grade, metastasis, and TP53 status. Interestingly, our insilico results strongly suggested that FAHD2B gene and protein interaction networks are associated with gliomas development both low and high grade.

Conclusion : Based on our findings, FAHD2B over-expression is linked to metastasis to other areas and generally has a poorer prognosis. When treating gliomas, it may be employed as a new prognostic indicator and therapeutic target.