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识别铜死亡相关亚型，建立预后模型，并描绘前列腺癌肿瘤微环境浸润特征。

Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer.

机构信息

Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Front Immunol. 2022 Sep 20;13:974034. doi: 10.3389/fimmu.2022.974034. eCollection 2022.

DOI:10.3389/fimmu.2022.974034
PMID:36203594
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9530990/
Abstract

Cuproptosis, Copper Induced Cell Death, is a newly defined type of programmed cell death, involving in the regulation of tricarboxylic acid (TCA) cycle. Dysfunction of cuproptosis induces cytotoxicity and influences the proliferation of multiple tumors. However, the direct prognostic effect of cuproptosis related genes and corresponding regulating mechanisms amid prostate cancer remains unknown. A multi-omics analysis strategy was adopted to explore the role of ten cuproptosis related genes in The Cancer Genome Atlas- Prostate Adenocarcinoma (TCGA-PRAD). Firstly, mRNA expression, Copy Number Variance (CNV), mutation, DNA methylation and prognostic power of the ten genes were illustrated. Based on transcriptomic data, we developed a novel prognostic model named the Cuproptosis-related gene score (CRGScore), Their biological functions were then detected by enrichment analysis and unsupervised cluster analysis. Following that, their correlation with Tumor Immune Microenvironment (TIME), immunotherapy, Biochemical Recurrence (BCR) and chemotherapeutic resistance were elaborated by relevant bioinformatics algorithms. Ten cuproptosis related genes exhibited extensive alteration of CNV and DNA methylation and showed significant influence on the prognosis of prostate cancer patients. These genes mainly enriched in E2F and G2M targets and mitosis pathways, Samples with high CRGScore showed enhancement resulting in the increased infiltration of T cell, B cell, NK cells. They also demonstrated close correlations with the BCR status, expression of eight immune checkpoints and chemotherapeutic resistances in prostate cancer. Our comprehensive analysis of CRGScore revealed an extensive regulatory mechanism by which they affect the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. We also determined the therapeutic liability of CRGScore in targeted therapy and immunotherapy. These findings highlight the crucial clinical implications of CRGScore and provide new ideas for guiding personalized immunotherapy strategies for patients with Pca.

摘要

铜死亡，铜诱导的细胞死亡，是一种新定义的程序性细胞死亡类型，涉及三羧酸（TCA）循环的调节。铜死亡功能障碍诱导细胞毒性，并影响多种肿瘤的增殖。然而，前列腺癌中铜死亡相关基因的直接预后效应及其相应的调节机制尚不清楚。本研究采用多组学分析策略，探讨了在癌症基因组图谱-前列腺腺癌（TCGA-PRAD）中十个铜死亡相关基因的作用。首先，展示了十个基因的 mRNA 表达、拷贝数变异（CNV）、突变、DNA 甲基化和预后能力。基于转录组数据，我们开发了一种新的预后模型，命名为铜死亡相关基因评分（CRGScore）。然后通过富集分析和无监督聚类分析检测它们的生物学功能。接下来，通过相关生物信息学算法阐述了它们与肿瘤免疫微环境（TIME）、免疫治疗、生化复发（BCR）和化疗耐药性的相关性。十个铜死亡相关基因表现出广泛的 CNV 和 DNA 甲基化改变，并对前列腺癌患者的预后有显著影响。这些基因主要富集在 E2F 和 G2M 靶标和有丝分裂途径中，CRGScore 高的样本显示出增强作用，导致 T 细胞、B 细胞、NK 细胞的浸润增加。它们还与前列腺癌的 BCR 状态、八个免疫检查点的表达和化疗耐药性密切相关。我们对 CRGScore 的综合分析揭示了它们影响肿瘤-免疫-基质微环境、临床病理特征和预后的广泛调节机制。我们还确定了 CRGScore 在靶向治疗和免疫治疗中的治疗相关性。这些发现强调了 CRGScore 的重要临床意义，并为指导前列腺癌患者的个性化免疫治疗策略提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/39358855b76d/fimmu-13-974034-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/17d3997cedda/fimmu-13-974034-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/68cba1ce07f0/fimmu-13-974034-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/ad6ce472ffdd/fimmu-13-974034-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/23e8d61535ee/fimmu-13-974034-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/48fa05482571/fimmu-13-974034-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/7b01714b4aa3/fimmu-13-974034-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/ebc3d0d963b9/fimmu-13-974034-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/f77613dcee41/fimmu-13-974034-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/15fb9088facf/fimmu-13-974034-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/39358855b76d/fimmu-13-974034-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/17d3997cedda/fimmu-13-974034-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/fa8b2b093197/fimmu-13-974034-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/781cc5e27ecd/fimmu-13-974034-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/68cba1ce07f0/fimmu-13-974034-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/ad6ce472ffdd/fimmu-13-974034-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/23e8d61535ee/fimmu-13-974034-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/48fa05482571/fimmu-13-974034-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/7b01714b4aa3/fimmu-13-974034-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/ebc3d0d963b9/fimmu-13-974034-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/f77613dcee41/fimmu-13-974034-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/15fb9088facf/fimmu-13-974034-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc19/9530990/39358855b76d/fimmu-13-974034-g012.jpg

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[1]
Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer.

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引用本文的文献

[1]
Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review).

Int J Oncol. 2025-9

[2]
Copper death combination therapy: the innovative frontier and challenges in prostate cancer treatment.

Cancer Biol Ther. 2025-12

[3]
Integrated machine learning based on cuproptosis and RNA methylation regulators to explore the molecular model of prostate cancer and provide novel insights to immunotherapy.

J Cancer. 2025-6-12

[4]
Cuproptosis as a therapeutic target in cancer: a Systematic Review and bibliometric analysis of the research landscape.

Front Oncol. 2025-5-16

[5]
Integrative analysis of cuproptosis-related lncRNAs: Unveiling prognostic significance, immune microenvironment, and copper-induced mechanisms in prostate cancer.

Cancer Pathog Ther. 2024-3-29

[6]
Disrupting CENP-N mediated SEPT9 methylation as a strategy to inhibit aerobic glycolysis and liver metastasis in colorectal cancer.

Clin Exp Metastasis. 2024-12

[7]
A pan-cancer cuproptosis signature predicting immunotherapy response and prognosis.

Heliyon. 2024-7-30

[8]
Machine learning-based integration develops a mitophagy-related lncRNA signature for predicting the progression of prostate cancer: a bioinformatic analysis.

Discov Oncol. 2024-7-29

[9]
Therapeutic and prognostic effect of disulfidptosis-related genes in lung adenocarcinoma.

Heliyon. 2024-6-29

[10]
LncRNA AP000842.3 Triggers the Malignant Progression of Prostate Cancer by Regulating Cuproptosis Related Gene NFAT5.

Technol Cancer Res Treat. 2024

本文引用的文献

[1]
A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma.

Genes (Basel). 2022-5-10

[2]
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