Oxidative stress reprograms benign prostatic hyperplasia microenvironments: insights from integrative multi-omics and...

Area of Science:

• * Multi-omics and machine learning integration in urological research.
• * Investigating cellular mechanisms of oxidative stress in disease.

Background:

• * Oxidative stress (OS) is increasingly linked to benign prostatic hyperplasia (BPH).
• * The specific cellular programs driving OS in BPH remain largely undefined.
• * This study aims to uncover OS-associated biomarkers and stromal cell states in BPH.

Purpose of the Study:

• * To identify novel biomarkers associated with oxidative stress in BPH.
• * To characterize the molecular and cellular states of stromal cells under OS in BPH.
• * To explore the potential of these findings for diagnostic and therapeutic strategies.

Main Methods:

• * Integrated bulk and single-cell RNA sequencing data from BPH and control samples.
• * Employed Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms.
• * Utilized in vitro experiments (cell culture, gene manipulation) and immunohistochemistry (IHC) for validation.

Main Results:

• * Identified 499 differentially expressed genes (DEGs) and 26 OS-associated DEGs.
• * Nominated ACOX2, CTSB, and SERPINF1 as upregulated hub genes with diagnostic potential (AUCs 0.828-0.880).
• * Discovered two BPH subtypes and characterized OS-related cellular trajectories, particularly in fibroblasts, with elevated ACOX2 expression and activity.

Conclusions:

• * ACOX2, CTSB, and SERPINF1 are nominated as candidate OS-associated markers in BPH.
• * A multi-omics signature for BPH stratification is proposed, requiring larger cohort validation.
• * Experimental validation supports an ACOX2-driven phenotype under OS, suggesting therapeutic avenues.