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Investigating the prostate stroma, this study found specific genes and pathways linked to aggressive prostate cancer. Analyzing the tumor microenvironment offers new insights into predicting cancer prognosis.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Prostate cancer prognosis is heterogeneous, with tumor microenvironment increasingly recognized for its role in progression.
  • Previous research primarily focused on tumor biomarkers, overlooking stromal contributions.

Purpose of the Study:

  • To examine whole transcriptome expression of the prostate stroma.
  • To identify associations between stromal gene expression and aggressive/lethal prostate cancer.
  • To investigate the prognostic value of the tumor microenvironment.

Main Methods:

  • RNA sequencing of 272 tumor-adjacent and 120 benign-adjacent prostate stromal samples.
  • Differential gene and pathway expression analysis based on Gleason score and lethal outcome.
  • Validation of a previously developed stromal gene signature for Gleason score.

Main Results:

  • Significant differential expression of 26 genes and 12 pathways in tumor-adjacent stroma comparing high- vs. low-Gleason scores.
  • Identification of 11 and 15 differentially expressed genes in tumor-adjacent and benign-adjacent stroma, respectively, for lethal vs. nonlethal prostate cancer.
  • Validation of a stromal gene signature associated with Gleason score.

Conclusions:

  • Stroma-specific genes and pathways are differentially enriched in high Gleason score and lethal prostate cancer.
  • Molecular investigation of the tumor microenvironment provides additional prognostic information.
  • Stromal transcriptome analysis is crucial for understanding prostate cancer aggressiveness.