Construction and validation of a RARRES3-based prognostic signature related to the specific immune microenvironment of pancreatic cancer

  • 0Cancer Institute, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

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Summary

This summary is machine-generated.

A novel 14-gene Pancreatic adenocarcinoma (PAAD) immune signature, TiME-score, predicts prognosis and guides immunotherapy. This signature, based on immune-related genes, highlights the tumor immune microenvironment

Area Of Science

  • Oncology
  • Immunology
  • Genomics

Background

  • The tumor immune microenvironment (TiME) is crucial for Pancreatic Ductal Adenocarcinoma (PAAD) prognosis.
  • The role of TiME-related genes in guiding individualized immunotherapy for PAAD remains unclear.

Purpose Of The Study

  • To construct and validate a prognostic signature based on TiME-related genes for PAAD.
  • To explore the potential of this signature in predicting immunotherapy response.

Main Methods

  • Correlation analysis of immune-related genes (IRGs) and transcription factors (TFs).
  • Consensus clustering to identify immune-related molecular subtypes.
  • Lasso-Cox regression to build the TiME-score prognostic signature.
  • Validation using ICGC dataset, single-cell sequencing (GSE197177), and PAAD mouse models.

Main Results

  • A 14-gene signature (TiME-score) was developed, reflecting immune microenvironment characteristics.
  • TiME-score hub genes showed distinct expression and immune cell infiltration differences between tumor and adjacent tissues.
  • High expression of RARRES3, a hub gene, correlated with worse prognosis and increased M1 macrophage infiltration.
  • In vivo validation in PAAD mouse models confirmed the signature's predictive accuracy.

Conclusions

  • The TiME-score serves as a reliable prognostic biomarker for PAAD.
  • This signature has the potential to guide personalized immunotherapy strategies for PAAD patients.