Construction and validation of a RARRES3-based prognostic signature related to the specific 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.