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Development of a hypoxia-responsive macrophage prognostic model using single-cell and bulk RNA sequencing in pancreatic cancer

  • 0Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Plos One +

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May 2, 2025

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May 2, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study developed a 13-gene hypoxia model for pancreatic ductal adenocarcinoma (PDAC) that predicts chemotherapy response and poor outcomes. The model highlights KRTCAP2 as a key biomarker for worse prognosis in pancreatic cancer.

Area Of Science

  • Oncology
  • Tumor Microenvironment Research
  • Genomic Biomarker Discovery

Background

  • Pancreatic ductal adenocarcinoma (PDAC) exhibits poor survival rates and resistance to therapies.
  • Hypoxia within the tumor microenvironment significantly impacts PDAC progression and treatment efficacy.

Purpose Of The Study

  • To develop a prognostic model integrating the dynamics of the hypoxic tumor microenvironment in PDAC.
  • To identify hypoxia-responsive genes and macrophage subsets critical for PDAC progression.

Main Methods

  • Integration of single-cell RNA sequencing (scRNA-seq) data with TCGA-PAAD database.
  • Construction and validation of a hypoxia-related prognostic model using survival analysis and regression methods.
  • Evaluation of the model's predictive power for chemotherapy sensitivity and overall survival.

Main Results

  • A 13-gene hypoxia-related prognostic model was developed, demonstrating independent predictive capability for chemotherapy response and outcomes.
  • The hypoxia model outperformed traditional clinicopathologic features in predicting patient prognosis.
  • Pan-cancer analysis confirmed the relevance of hypoxia-related genes, identifying KRTCAP2 as a biomarker for poor prognosis and reduced immune infiltration.

Conclusions

  • The developed hypoxia-related model holds significant prognostic potential for pancreatic cancer.
  • This research offers novel therapeutic targets to improve outcomes in pancreatic cancer patients.