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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
The Emerging Role of MTHFD Family Genes in Regulating the Tumor Immunity of Oral Squamous Cell Carcinoma
Wei Wang1, Wenli Gu1, Hai Tang1
1Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.
Objective:
To investigate the function and regulatory mechanisms of methylenetetrahydrofolate dehydrogenase (MTHFD) family genes in oral squamous cell carcinoma (OSCC), especially focus on their regulating role in tumor immunity.
Methods:
The publicly available data from the TCGA database were used to investigate the expression pattern and regulatory role of MTHFD family genes in OSCC. More importantly, the involvement of MTHFD family genes in tumor immunity was investigated in terms of immune and stromal cell infiltration in tumor microenvironment, tumor-infiltrating immune cells, and immunomodulatory genes (e.g., immunoinhibitory genes and immunostimulatory genes). Statistical analysis was performed using R software packages and public web servers.
Results:
MTHFD family genes were considerably upregulated in OSCC as compared with normal oral tissue. Patients with high MTHFD2 expression presented worse survival outcomes than those with low MTHFD2 expression. Functional enrichment analysis showed that the top 100 positively and negatively correlated genes of the MTHFD family genes were significantly enriched in several KEGG pathways, including cell cycle, spliceosome, DNA replication, and Th17 cell differentiation. As a result of tumor immunity analysis, MTHFD2L expression was found to be negatively related to the Estimate-Stromal-Immune score in OSCC; however, there was no statistical significance between the Estimate-Stromal-Immune score and MTHFD1, MTHFD1L, or MTHFD2 in OSCC. Additionally, MTHFD family genes were found to be significantly positively correlated with tumor-infiltrating immune cells, including Treg and Th17 cells. Moreover, MTHFD family genes were significantly correlated with several immune inhibitory genes such as CD274 and CTLA4 and several immune-stimulatory genes such as CXCL12, CXCR4, and TMIGD2.
Conclusion:
Given the expression pattern, prognostic value, biological functions, and involvement in tumor immunity, MTHFD family genes could serve as potential therapeutic biomarkers in targeting tumor immunity in oral cancer.
Insights
Methylenetetrahydrofolate dehydrogenase (MTHFD) family genes are upregulated in oral squamous cell carcinoma (OSCC), impacting patient survival and tumor immunity. These MTHFD genes may serve as therapeutic targets for oral cancer immunotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with complex regulatory mechanisms.
- Methylenetetrahydrofolate dehydrogenase (MTHFD) family genes play crucial roles in cellular metabolism and have been implicated in various cancers.
Purpose of the Study:
- To investigate the function and regulatory mechanisms of MTHFD family genes in OSCC.
- To explore the role of MTHFD family genes in regulating tumor immunity within the OSCC microenvironment.
Main Methods:
- Utilized publicly available data from The Cancer Genome Atlas (TCGA) database for OSCC analysis.
- Analyzed MTHFD gene expression, correlation with patient survival, immune cell infiltration, and immunomodulatory gene expression.
- Performed statistical analysis using R software packages and public web servers.
Main Results:
- MTHFD family genes were significantly upregulated in OSCC tissues compared to normal tissues.
- High MTHFD2 expression correlated with poorer patient survival outcomes.
- MTHFD family genes showed significant positive correlations with tumor-infiltrating immune cells (e.g., Treg, Th17) and immune-related genes (e.g., CD274, CTLA4, CXCL12).
Conclusions:
- MTHFD family genes exhibit significant roles in OSCC progression and immune modulation.
- These genes demonstrate potential as prognostic biomarkers and therapeutic targets for enhancing anti-tumor immunity in oral cancer.
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