Disulfidptosis-related subtype and prognostic signature in prostate cancer

Zhen Kang ^1,2, Zheng-Hua Wan ^1,2, Rui-Cheng Gao ^1,2

⁰Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.

Biology Direct +

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October 24, 2024

View abstract on PubMed

Summary

Disulfidptosis, a cell death mechanism, is linked to prostate cancer (PCa). This study identifies disulfidptosis-related genes as potential biomarkers for PCa classification, prognosis, and immune microenvironment modulation, offering new therapeutic avenues.

Area Of Science

Oncology
Cell Biology
Biochemistry

Background

Disulfidptosis is a cell death pathway triggered by disulfide accumulation in SLC7A11-high cells under glucose deprivation.
The role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and tumor microenvironment regulation is not well understood.

Purpose Of The Study

To investigate the role of DRGs in PCa classification and tumor microenvironment.
To develop a prognostic model for PCa based on DRGs.

Main Methods

Analysis of DRG expression and mutation landscape in PCa.
In vitro experiments assessing SLC7A11 expression and the effect of BAY-876.
Unsupervised clustering and machine learning to identify DRG-based risk signatures.
Evaluation of tumor immune microenvironment and immunotherapy sensitivity in different risk groups.
Validation using single-cell sequencing, qPCR, and western blot.

Main Results

BAY-876 inhibited viability in SLC7A11-high PCa cells.
PCa patients were classified into two clusters (A and B) based on DRGs.
A four-gene risk signature was developed and validated.
Cluster B (lower risk) showed better prognosis, higher immune infiltration, and greater immunotherapy sensitivity compared to Cluster A.
A nomogram integrating DRGs and clinical features was created for prognosis assessment.

Conclusions

DRGs are implicated in PCa classification and prognosis.
A disulfidptosis-related prognostic model shows promise for PCa management.
DRGs may serve as therapeutic targets for PCa.