Zhong Haitao, Lai Yiming, Ouyang Wenhao, Yu Yunfang, Wu Yongxin, He Xinxin, Zeng Lexiang, Qiu Xueen, Chen Peixian, Li Lingfeng, Zhou Jie, Luo Tianlong, Huang Hai
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
Cancer Pathog Ther. 2024 Mar 29;3(1):48-59. doi: 10.1016/j.cpt.2024.03.004. eCollection 2025 Jan.
Long non-coding ribonucleic acids (lncRNAs) regulate messenger RNA (mRNA) expression and influence cancer development and progression. Cuproptosis, a newly discovered form of cell death, plays an important role in cancer. Nonetheless, additional research investigating the association between cuproptosis-related lncRNAs and prostate cancer (PCa) prognosis is required.
Sequencing data and copy number variant data were obtained from 492 patients with PCa from The Cancer Genome Atlas (TCGA) Program. Prognostic models of PCa based on cuproptosis-related lncRNAs were constructed using a multi-level attention graph neural network (MLA-GNN) deep learning algorithm. Immune escape scoring was performed using Tumor Immune Dysfunction and Exclusion. Cellular experiments were conducted to explore the correlation between key lncRNAs and cuproptosis.
Data from 492 patients with PCa were randomized into two groups at a 1:1 ratio. Prognostic modeling was successfully established using MLA-GNN. Survival analysis suggested that patients could be divided into high- and low-risk groups according to model scores and that there was a significant difference in disease-free survival (DFS) ( < 0.01). The area under the receiver operating characteristic (ROC) curve (AUC) indicated a strong predictive performance for the model, with AUCs of 0.913, 0.847, and 0.863 for the training group and 0.815, 0.907, and 0.866 for the test group at 12, 36, and 60 months, respectively. The immune escape score and immune microenvironment analysis suggested that the high-risk group corresponded to a stronger immune escape and a poorer immune microenvironment ( < 0.05). Cellular experiments revealed that the expression of all six key lncRNAs was upregulated in the presence of copper ion carriers ( < 0.05).
This study identified cuproptosis-related lncRNAs that were strongly associated with PCa prognosis. Key lncRNAs could affect copper metabolism and may serve as new therapeutic targets.
长链非编码核糖核酸(lncRNAs)调节信使核糖核酸(mRNA)表达,并影响癌症的发生和发展。铜死亡是一种新发现的细胞死亡形式,在癌症中起重要作用。然而,需要更多研究来调查与铜死亡相关的lncRNAs与前列腺癌(PCa)预后之间的关联。
从癌症基因组图谱(TCGA)项目的492例PCa患者中获取测序数据和拷贝数变异数据。使用多级注意力图神经网络(MLA-GNN)深度学习算法构建基于与铜死亡相关的lncRNAs的PCa预后模型。使用肿瘤免疫功能障碍和排除法进行免疫逃逸评分。进行细胞实验以探索关键lncRNAs与铜死亡之间的相关性。
492例PCa患者的数据以1:1的比例随机分为两组。使用MLA-GNN成功建立了预后模型。生存分析表明,根据模型评分,患者可分为高风险组和低风险组,无病生存期(DFS)存在显著差异(<0.01)。受试者工作特征(ROC)曲线下面积(AUC)表明该模型具有很强的预测性能,训练组在12、36和60个月时的AUC分别为0.913、0.847和0.863,测试组分别为0.815、0.907和0.866。免疫逃逸评分和免疫微环境分析表明,高风险组对应更强的免疫逃逸和更差的免疫微环境(<0.05)。细胞实验显示,在存在铜离子载体的情况下,所有六个关键lncRNAs的表达均上调(<0.05)。
本研究确定了与PCa预后密切相关的与铜死亡相关的lncRNAs。关键lncRNAs可能影响铜代谢,并可能成为新的治疗靶点。