Immune Microenvironment and Response in Prostate Cancer Using Large Population Cohorts.

Area of Science:

• Oncology
• Immunology
• Bioinformatics

Background:

• The immune microenvironment significantly influences prostate cancer (PCa) progression.
• Previous research has not fully elucidated the complex immune landscape within PCa.

Purpose of the Study:

• To comprehensively explore the PCa immune microenvironment.
• To develop a novel immune-related risk score (IRS) signature for predicting PCa prognosis and immunotherapy response.

Main Methods:

• Utilized ssGSEA algorithm to analyze expression levels of 53 immune terms across a combined PCa cohort (1,597 samples).
• Employed random forest analysis to select top 10 immune terms for IRS calculation.
• Performed consensus clustering to stratify patients into distinct IRS clusters.

Main Results:

• Developed an IRS signature demonstrating high predictive potential for PCa prognosis.
• High IRS group associated with increased immunotherapy response factors.
• Identified three IRS clusters with differential clinical outcomes and immunotherapy response rates.
• Discovered differential expression of key genes (e.g., VGLL3, ANPEP, CD38) across IRS clusters.
• CMap analysis identified five compounds targeting the IRS signature.

Conclusions:

• The developed IRS signature is a valuable tool for assessing PCa prognosis.
• The IRS signature effectively predicts immunotherapy response rates in PCa patients.
• IRS clustering provides insights into distinct patient subgroups with varying clinical trajectories and treatment sensitivities.