Abstract
Abstract Objective To investigate methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, biological function, and correlation with head and neck squamous cell carcinoma (HNSCC) patient’s prognosis. Methods The relative expression levels of MTHFD2 gene mRNA in tumor tissues of HNSCC and adjacent normal tissues were analyzed in the Cancer Genome Atlas and oncomine database. MTHFD2 protein relative expression in tumor tissue of HNSCC patients was analyzed in human proteome database. Protein–protein interaction (PPI) network of MTHFD2 and correlated genes were constructed in STRING database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway of MTHFD2 and relevant proteins involved in the PPI network was enriched. The Tumor Immune Estimation Resource database was used to analyze the relationship between MTHFD2 expression and immune infiltration. Overall survival (OS) and progression-free survival (PFS) for MTHFD2 high and low expression groups were investigated in the Kaplan–Meier Plotter database. Results In HNSCC, MTHFD2 mRNA relative expression level in tumor tissue was significantly higher than the corresponding normal tissue with statistical difference (p < 0.05). In the PPI network, 21 protein coding genes were involved in the network with 124 edges, which indicated that the enrichment was significant (p < 0.05). MTHFD2 and PPI network involved genes were mainly enriched in tetrahydrofolate metabolic process, one-carbon metabolic process biological process. In KEGG pathway, MTHFD2 and PPI network involved genes were mainly enriched in one-carbon pool by folate, metabolic pathways, glyoxylate, and dicarboxylate metabolism, and carbon metabolism. The relative expression level of MTHFD2 gene was correlated with immune infiltration of macrophage (r = 0.712, p < 0.05), neutrophil (r = 0.158, p < 0.05), dendritic cell (r = 0.1825, p < 0.05), and CD4+ T lymph cell (r = 0.1825, p < 0.05). HNSCC patients with high expression MTHFD2 had low OS compared to low expression cases (hazard ratio = 1.53, 95% CI: 1.16–2.02, p < 0.05). Conclusion MTHFD2 is overexpressed in HNSCC and correlated with patient’s prognosis. MTHFD2 maybe a potential target for HNSCC target treatment and provides a possible direction for the research and development of related targeted drugs.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor globally, with more than 550,000 cases and 300,000 deaths each year [1]
methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) and Protein–protein interaction (PPI) network involved genes were mainly enriched in tetrahydrofolate metabolic process, one-carbon metabolic process biological process
The relative expression level of MTHFD2 gene was correlated with immune infiltration of macrophage (r = 0.712, p < 0.05), neutrophil (r = 0.158, p < 0.05), dendritic cell (r = 0.1825, p < 0.05), and CD4+ T lymph cell (r = 0.1825, p < 0.05)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor globally, with more than 550,000 cases and 300,000 deaths each year [1]. MTHFD2 is overexpressed in HNSCC 99 chemotherapy, and biotherapy) are most applied treatment methods clinically [3]. We found that MTHFD2 was over expressed in malignant carcinomas including HNSCC and correlated with patient’s prognosis. MTHFD2 maybe a potential target for HNSCC target treatment and provide a possible direction for the research and development of related targeted drugs. The present work had limitations: (i) most of the findings are based on bioinformatics analysis, which need verification by cell experiments; and (ii) the conclusion of the present work especially on survival needs further confirmation by clinical data
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