Construction and validation of a folate metabolism-related gene signature for predicting prognosis in HNSCC

Area of Science:

• Oncology
• Metabolic Pathways
• Immunology

Background:

• Metabolic reprogramming is a key feature in tumor and immune cell development.
• Identifying metabolic enzymes linked to prognosis in head and neck squamous cell carcinomas (HNSCC) is crucial.

Purpose of the Study:

• To identify metabolic enzymes associated with clinical prognosis in HNSCC.
• To investigate the role of folate metabolism in HNSCC development and immune escape.

Main Methods:

• Cox regression analysis was used to construct folate metabolism scores from candidate genes.
• Gene Ontology (GO), KEGG, Gene Set Variation Analysis (GSVA), and single-sample Gene Set Enrichment Analysis (ssGSEA) were employed for functional enrichment.
• Immune cell infiltration was analyzed using EPIC, MCPcounter, and xCell, with data visualized using the "IOBR" software package.

Main Results:

• A six-gene folate metabolism signature (MTHFD1L, MTHFD2, SHMT2, ATIC, MTFMT, MTHFS) accurately predicts folate metabolism levels in HNSCC.
• Folate metabolism reprogramming impacts CD8+ T cell infiltration and promotes immune escape via the MIF signaling pathway.
• SHMT2 inhibits CD8+ T cell infiltration and induces immune escape by regulating the MIF/CD44 signaling axis, promoting HNSCC progression.

Conclusions:

• A novel six-gene folate metabolic signature effectively assesses prognosis and immune status in HNSCC patients.
• SHMT2 is identified as a key molecule in folate metabolic reprogramming, significantly contributing to HNSCC development and immune escape.