Integrative analysis of cuproptosis-related IncRNAs:Unveiling prognostic significance,immune microenvironment,and copper-induced mechanisms in prostate cancer  

作　　者：Haitao Zhong Yiming Lai Wenhao Ouyang Yunfang Yu Yongxin Wu Xinxin He Lexiang Zeng Xueen Qiu Peixian Chen Lingfeng Li Jie Zhou Tianlong Luo Hai Huang 

机构地区：[1]Department of Urology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,China [2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou Guangdong510120,China [3]Guangdong Provincial Clinical Research Center for Urological Diseases,Sun Yat-sen Memorial Hospital Sun Yat-sen University,Guangzhou,Guangdong 510120,China [4]Department of Uroogy,The FithAflated Hospitalf Xinjiang Medical Universiy,UrumqiXijang30011,China [5]Department of Medical Oncology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,China [6]Faculty of Medicine,Macao University of Science and Technology,Avenida WaiLong,Taipa,Macao 99978,China [7]Department of Pathology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,China [8]Department of Emergency,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,China [9]Department of Urology,The Sixth Affliated Hospitalof Guangzhou Medical University,Qingyuan People's Hospital,Qingyuan Guangdong 511518,China

出　　处：《Cancer Pathogenesis and Therapy》2025年第1期48-59,共12页癌症发生与治疗(英文)

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.82372912,81802527,81972471,82073408,81974395,and 82173036);National Key Research and Development Program of China(Nos.2022YFC3602900 and 2022YFC3602904);BeijingBethune CharitableFoundation(Nos.mnzl202001 and mnzl202026);Guangzhou Science and Technology Project(Nos.202206010078 and 202201020574);Sun Yat-sen University Clinical Research 5010 Program(Nos.2018007 and 2019005);Sun Yat-sen Clinical Research Cultivating Program(No.SYS-C-201801);Guangdong Medical Science and Technology Program(No.A2020558);Tencent Charity Foundation(No.7670020025);Scientific Research Launch Project of Sun Yat-sen Memorial Hospital(No.YXQH202209);GuangdongBasicand AppliedBasicResearchFoundation(No.2019A1515011437);International Science and Technology Cooperation Project Plan of Guangdong Province(No.2021A0505030085);Guangzhou Science and Technology Key R&D Project(No.202206010117);Beijing CSCO Clinical Oncology Research Foundation(No.Y-tongshu2021/ms-0162);Guangdong Provincial Clinical Research Center for Urological Diseases(No.2020B1111170006);Guangdong Science and Technology Department(No.2020B1212060018);open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University,Qingyuan People's Hospital.

摘　　要：Background: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 cuproptosisrelated IncRNAs and prostate cancer(PCa)prognosis is required.Methods: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 IncRNAs 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.Results: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)(P<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(P<0.05).Cellular experiments revealed that the expression of all six key lncRNAs was upregulated in the presence of copper ion carriers(P<0.05).Conclusions:This study identified cuproptosis-related IncRNAs that were strongly associated with PCa prognosis.Key lncRNAs could affect copper metabolism and may serve as new therapeutic targets.

关 键 词：Prostate cancer Cuproptosis Deep learning IncRNAs 

分 类 号：R737.25[医药卫生—肿瘤]