Linking Targeted Pancreatic Cancer Genes With Metabolic Disorders: A Cross-Species Translational Pathway

Area of Science:

• Oncology
• Metabolic Disorders
• Immunology

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with limited treatment options.
• PDAC is increasingly associated with metabolic dysfunctions like obesity, inflammation, and diabetes.

Purpose of the Study:

• To investigate the molecular interplay between PDAC-associated genes and metabolic disorder pathways.
• To identify key genes and pathways linking PDAC and metabolic dysregulation.

Main Methods:

• Analysis of bulk and single-cell RNA-Seq datasets from human and murine tissues.
• Examination of key gene expression patterns (ITGAM, PECAM1, CCL5, STAT1, STAT2, CD44).
• Functional analyses including KEGG pathway enrichment, protein-protein interaction networks, and qPCR validation.

Main Results:

• High expression of PDAC markers observed in obese human and mouse models.
• Single-cell clusters showed transcriptional profiles linked to metabolic dysregulation in PDAC.
• Upregulation of ITGAM, CCL5, CXCL10, STAT1, and STAT2 confirmed in obese individuals, indicating an immunometabolic axis.

Conclusions:

• Upregulation of PDAC recurrence genes is strongly associated with activated metabolic pathways (obesity, diabetes, inflammation).
• Consistent cross-species expression patterns suggest potential therapeutic targets.
• Inhibiting these metabolic pathways post-surgery may reduce PDAC fatality.