A Potential Target for Suppressing Pancreatic Cancer: PDGFRB Regulated by DNA Methylation

Area of Science:

• Genetics and Genomics
• Cancer Biology
• Epigenetics

Background:

• Pancreatic cancer (PC) has a high mortality rate and limited treatment options.
• The roles of DNA methylation and protein Quantitative Trait Loci (pQTL) in PC development require further investigation.

Purpose of the Study:

• To investigate the causal relationship between gene expression, DNA methylation, and pancreatic cancer risk.
• To identify potential therapeutic targets for PC by integrating genetic and epigenetic data.

Main Methods:

• Mendelian randomization (MR) analysis using large-scale GWAS, mQTL, and pQTL datasets.
• Sensitivity analyses to assess robustness against heterogeneity and pleiotropy.
• Single-cell RNA sequencing and mediation analysis to explore regulatory mechanisms.

Main Results:

• Higher Platelet-Derived Growth Factor Receptor Beta (PDGFRB) expression was associated with reduced PC risk (OR ≈ 0.92).
• DNA methylation at cg11042320 was found to mediate approximately 98% of this association.
• PDGFRB expression was enriched in pancreatic islets, suggesting a protective role.

Conclusions:

• PDGFRB acts as a protective factor against pancreatic cancer, regulated by cg11042320 methylation.
• This study establishes a causal pathway from methylation to gene expression to PC risk.
• PDGFRB and its epigenetic regulation represent potential targets for novel PC therapies.