# Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer

## TL;DR

This study identifies molecular changes linked to a specific stromal response in prostate cancer, which could help predict outcomes and guide treatment.

## Contribution

The study reveals a distinct molecular signature associated with a histologically overt stromal response in prostate cancer.

## Key findings

- 1263 genes showed significantly higher expression in patients with a HOST-response.
- Seven hub genes were identified as highly interconnected in the protein–protein interaction network.
- Alterations in cell division and inflammation-related pathways were observed in patients with a HOST-response.

## Abstract

Prostate cancer has substantial heterogeneity in clinical outcomes and therapeutic responses, posing challenges in predicting disease progression and tailoring treatment strategies. Recent studies have highlighted the potential prognostic value of evaluating the tumor microenvironment, including the presence of a histologically overt stromal response (HOST-response) characterized by peri-glandular stromal changes and architectural distortions. This retrospective study examined patient records from The Cancer Genome Atlas database to identify genomic alterations associated with the HOST-response in prostate cancer. Among 348 patients who underwent radical prostatectomy, 160 (45.98%) were identified as having a HOST-response. A gene expression analysis revealed 1263 genes with significantly higher expression in patients with a HOST-response. A protein–protein interaction network analysis identified seven hub genes (KIF2C, CENPA, CDC20, UBE2C, ESPL1, KIF23, and PLK1) highly interconnected in the network. A functional enrichment analysis revealed alterations in the cell division, cytoskeletal organization, cytokinesis, and interleukin-16 signaling pathways in patients with a HOST-response, suggesting dysregulated proliferation and inflammation. The distinct molecular signature associated with the HOST-response provides insights into the tumor–stroma interactions driving adverse outcomes and potential targets for tailored therapeutic interventions in this subset of patients with prostate cancer.