Deciphering the Heterogeneity of Pancreatic Cancer: DNA Methylation-Based Cell Type Deconvolution Unveils Distinct...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is a complex cancer with a poorly understood tumor microenvironment (TME).
• Existing bulk omics data limit understanding of immune and stromal cell roles in PDAC progression and treatment response.

Purpose of the Study:

• To analyze epigenomic and transcriptomic data for PDAC patients.
• To characterize the immune composition of the TME and identify gene co-expression networks.

Main Methods:

• Utilized Cancer Genome Atlas Pancreatic Adenocarcinoma (TCGA-PAAD) cohort data.
• Performed genome-wide DNA methylation profiling and transcriptomic analysis.
• Applied hierarchical deconvolution, epigenetic age estimation, and weighted gene co-expression network analysis (WGCNA).

Main Results:

• Identified two distinct PDAC groups based on methylation profiles, with Group 2 showing higher purity and more KRAS mutations.
• Discovered three TME subtypes: hypo-inflamed, myeloid-enriched, and lymphoid-enriched (T-cell predominant).
• WGCNA modules confirmed immune clusters and highlighted enrichment in immune regulatory pathways.

Conclusions:

• An integrative epigenomic-transcriptomic approach provides a framework for PDAC patient stratification based on TME.
• Findings offer insights for discovering biomarkers and advancing precision immunotherapies for pancreatic cancer.