Exploring CD4+ T Cell-Mediated Metabolism in Serous Ovarian Cancer via Mendelian Randomization and Single-Cell...

Area of Science:

• Oncology
• Immunology
• Metabolomics

Background:

• Serous ovarian cancer (SOC) remains a significant health challenge.
• Understanding the etiological factors and underlying mechanisms of SOC is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the causal relationship between 1-palmitoyl-GPG (16:0) and serous ovarian cancer (SOC).
• To explore the potential mediating role of naive CD4+ T cell proportions and metabolic gene expression in this relationship.

Main Methods:

• Two-sample Mendelian randomization (MR) and mediation analyses were performed.
• Single-cell RNA sequencing, immune infiltration analysis, and machine learning algorithms (Lasso, CatBoost, SHAP) were employed.
• Gene expression of palmitoyl-CoA synthesis pathways in CD4+ T cells was examined.

Main Results:

• 1-palmitoyl-GPG (16:0) showed a causal effect on SOC, mediated by naive CD4+ T cells and potentially by metabolic gene expression (e.g., PIGB) in CD4+ T cells.
• Key palmitoyl-CoA synthesis genes, including PIGB, were highly expressed in CD4+ T cells, influencing SOC development.
• Machine learning models demonstrated predictive performance, with PIGB identified as a key driver in SOC prediction.

Conclusions:

• A causal link between 1-palmitoyl-GPG (16:0) and SOC, mediated by naive CD4+ T cells and specific synthesis genes, was established.
• Findings offer insights into the metabolic and immunological underpinnings of SOC.
• Potential therapeutic targets for SOC intervention were identified.