# Exploring the Molecular Mechanism and Role of Glutathione S-Transferase P in Prostate Cancer

## TL;DR

This study explores how Glutathione S-transferase P (GSTP) in prostate cancer affects disease risk and identifies its role in reducing cancer risk through genetic and molecular mechanisms.

## Contribution

The study identifies GSTP1 as a potential diagnostic biomarker and demonstrates its causal protective role in prostate cancer through Mendelian randomization and single-cell analysis.

## Key findings

- GSTP in Glutathione metabolism reduces prostate cancer risk according to Mendelian randomization analysis.
- Low expression of GSTP1 gene is associated with prostate cancer and improves diagnostic accuracy.
- High GSTP1 expression in epithelial cells correlates with P53 pathway activation and apoptosis in prostate cancer.

## Abstract

Aims: To investigate the effect of Glutathione metabolism in prostate cancer pathogenesis. Background: There is growing evidence that Glutathione metabolism plays an important role in prostate cancer, with genes encoding key enzymes in this pathway potentially serving as diagnostic or prognostic biomarkers. Objective: To explore whether there is a causal relationship between key enzymes in the Glutathione metabolism and prostate cancer, and to further investigate the molecular mechanisms and roles of the genes encoding their proteins in relation to prostate cancer. Method: Transcriptomic datasets from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs) and enriched pathways in prostate cancer versus normal tissues. Two-sample bidirectional Mendelian randomization (MR) was employed to assess causal relationships between Glutathione metabolic enzymes (exposure) and prostate cancer risk (outcome). Immune infiltration analysis and LASSO regression were performed to construct a diagnostic model. Single-cell RNA sequencing (scRNA-seq) data were utilized to elucidate cell-type-specific expression patterns and functional associations of target genes. Result: The results of two-sample bidirectional MR showed that Glutathione S-transferase P (GSTP) in Glutathione metabolism could reduce the risk of prostate cancer. The Glutathione S-transferase Pi-1 (GSTP1) gene was lowly expressed in prostate cancer and was able to diagnose prostate cancer more accurately. Single-cell analysis showed that the high expression of GSTP1 in prostate cancer epithelial cells was closely associated with the upregulation of the P53 pathway and apoptosis. Conclusions: Our study reveals that GSTP in Glutathione metabolism reduces the risk of prostate cancer and further analyzes the genetic association and mechanism of action between GSTP1 and prostate cancer.