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基于 Gleason 分级和铜死亡相关基因建立前列腺癌预后风险模型。

Establishment of a prognostic risk model for prostate cancer based on Gleason grading and cuprotosis related genes.

机构信息

Department of Urology, Hebei Medical University, Shijiazhuang, China.

Department of Urology, Qinhuangdao First Hospital, No. 258 Wenhua Road, Haigang District, Qinhuangdao, 066000, China.

出版信息

J Cancer Res Clin Oncol. 2024 Aug 1;150(8):376. doi: 10.1007/s00432-024-05899-9.

DOI:10.1007/s00432-024-05899-9
PMID:39085482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11291559/
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.

摘要

简介

前列腺癌(PCa)在老年男性中较为常见,通过格里森分级系统进行诊断。本研究探讨了杯状细胞死亡(一种独特的细胞死亡类型)与格里森评分一起在 PCa 中的未被研究的预后价值。

方法

我们使用 TCGA-PRAD 数据的 NMF 对前列腺癌(PCa)中的 Cuprotosis 相关基因(CRGs)进行了探索,用于患者分类,并使用 WGCNA 将基因与格里森评分和预后联系起来。通过 LASSO Cox 回归构建风险模型。在 PC-3 细胞中敲低 STX3,分析其对细胞行为和小鼠肿瘤生长的影响,突出了其潜在的治疗作用。

结果

我们确定了五个对预后风险模型至关重要的基因,较高的风险评分表明预后较差。生存分析和 ROC 曲线在 TCGA-PRAD 和 GSE70769 数据集上证实了该模型的预测准确性。STX3 是一个关键的不良预后因素,其敲低显著降低了 PC-3 细胞的 mRNA 和蛋白水平,损害了其功能。在体内,PC-3 细胞中 STX3 的敲低导致裸鼠中的肿瘤明显缩小,突出了其潜在的治疗价值。

结论

我们的预后模型使用与格里森评分相关的五个基因,可有效预测前列腺癌的结局,为治疗策略提供了一个新的角度。

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