JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Molecular Pathway and Immune Profile Analysis of IPMN-Derived Versus PanIN-Derived Pancreatic Ductal Adenocarcinomas

  • 0Department of Gastrointestinal (GI) Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
International Journal of Molecular Sciences +

|

December 17, 2024

|

December 17, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Molecular signatures distinguish pancreatic ductal adenocarcinoma (PDAC) originating from intraductal papillary mucinous neoplasms (IPMN) versus pancreatic intraepithelial neoplasia (PanIN). IPMN-derived PDAC shows distinct metabolic pathways, unlike PanIN-derived PDAC enriched in inflammatory and immune pathways.

Area Of Science

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background

  • Intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic cysts with malignant potential, often progressing to pancreatic ductal adenocarcinoma (PDAC).
  • Distinguishing between IPMN-derived PDAC and PDAC from other pathways (e.g., pancreatic intraepithelial neoplasia, PanIN) is crucial for clinical management and surveillance.
  • Identifying molecular signatures can aid in predicting IPMN progression and developing targeted therapies.

Purpose Of The Study

  • To identify molecular signatures that differentiate PDAC with IPMN origin from PDAC arising via the PanIN pathway.
  • To uncover novel molecular pathways associated with IPMN-derived PDAC for potential biomarker development.
  • To guide biomarker strategies for early detection and treatment of PDAC.

Main Methods

  • Analysis of whole transcriptome sequencing data from 66 PDAC cases (16 IPMN-derived, 50 PanIN-derived) from the ORIEN network.
  • Differential gene expression and pathway analysis using Gene-Set Enrichment Analysis (GSEA) and Pathway Analysis with Down-weighted Genes (PADOG).
  • Immune profiling using the Tumor-Immune Microenvironment Deconvolution (TIMEx) web portal.

Main Results

  • PanIN-derived PDAC tumors showed enrichment in inflammatory and immune-related pathways (e.g., complement, hedgehog signaling, coagulation, inflammatory response, EMT, KRAS signaling, IFN-gamma).
  • IPMN-derived tumors were enriched in metabolic and energy-generating pathways (e.g., oxidative phosphorylation, unfolded protein response, fatty acid metabolism).
  • Significantly upregulated genes in IPMN-derived PDAC included MUC2 and GKN2; this metabolic signature correlated with early-stage, long-survival PDAC cases in TCGA.

Conclusions

  • IPMN-derived and PanIN-derived PDAC exhibit distinct molecular profiles, particularly in immune and metabolic pathway expression.
  • These findings suggest different biological underpinnings for PDAC arising from distinct precursor lesions.
  • Further validation is needed to translate these molecular differences into effective biomarker-based strategies for PDAC detection and treatment.

Keywords: