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Establishment of a Prognostic Risk Model for Prostate Cancer Based on Gleason Grading and Cuprotosis Related Genes

Overview
Specialty Oncology
Date 2024 Jul 31
PMID 39085482
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Abstract

Introduction: Prostate cancer (PCa) is common in aging males, diagnosed via the Gleason grading system. The study explores the unexamined prognostic value of cuprotosis, a distinct cell death type, alongside Gleason grades in PCa.

Methods: We explored Cuprotosis-related genes (CRGs) in prostate cancer (PCa), using NMF on TCGA-PRAD data for patient classification and WGCNA to link genes with Gleason scores and prognosis. A risk model was crafted via LASSO Cox regression. STX3 knockdown in PC-3 cells, analyzed for effects on cell behaviors and tumor growth in mice, highlighted its potential therapeutic impact.

Results: We identified five genes crucial for a prognostic risk model, with higher risk scores indicating worse prognosis. Survival analysis and ROC curves confirmed the model's predictive accuracy in TCGA-PRAD and GSE70769 datasets. STX3 was a key adverse prognostic factor, with its knockdown significantly reducing mRNA and protein levels, impairing PC-3 cell functions. In vivo, STX3 knockdown in PC-3 cells led to significantly smaller tumors in nude mice, underscoring its potential therapeutic value.

Conclusion: Our prognostic model, using five genes linked to Gleason scores, effectively predicts prostate cancer outcomes, offering a novel treatment strategy angle.

References
1.
Chen J, Guccini I, Di Mitri D, Brina D, Revandkar A, Sarti M . Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer. Nat Genet. 2018; 50(2):219-228. PMC: 5810912. DOI: 10.1038/s41588-017-0026-3. View

2.
Jemal A, Ma J, Siegel R, Fedewa S, Brawley O, Ward E . Prostate Cancer Incidence Rates 2 Years After the US Preventive Services Task Force Recommendations Against Screening. JAMA Oncol. 2016; 2(12):1657-1660. DOI: 10.1001/jamaoncol.2016.2667. View

3.
Nwosu V, Carpten J, Trent J, Sheridan R . Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease. Hum Mol Genet. 2001; 10(20):2313-8. DOI: 10.1093/hmg/10.20.2313. View

4.
Nan H, Han L, Ma J, Yang C, Su R, He J . STX3 represses the stability of the tumor suppressor PTEN to activate the PI3K-Akt-mTOR signaling and promotes the growth of breast cancer cells. Biochim Biophys Acta Mol Basis Dis. 2018; 1864(5 Pt A):1684-1692. DOI: 10.1016/j.bbadis.2018.01.031. View

5.
Gaujoux R, Seoighe C . A flexible R package for nonnegative matrix factorization. BMC Bioinformatics. 2010; 11:367. PMC: 2912887. DOI: 10.1186/1471-2105-11-367. View