A cuproptosis-related LncRNA signature: Integrated analysis associated with biochemical recurrence and immune landscape in prostate cancer

Frontiers in Genetics

Genetics

Xu Yang¹  Guankai Huang¹  Xiaopeng Mao¹  Lei Ren¹  Hansen Lin¹  Weifeng Wang¹  Jincheng Pan¹  Zixiong Liu² 

[1] Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China;Department of Urology, The Seventh Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China;

关键词: cuproptosis;    prostate cancer;    lncRNA;    biochemical recurrence;    prognostic model;    immune cell infiltration;   

DOI  :  10.3389/fgene.2023.1096783

 received in 2022-11-12, accepted in 2023-02-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: As a new form of regulated cell death, cuproptosis differs profoundly from apoptosis, ferroptosis, pyroptosis, and necroptosis. The correlation between cuproptosis and long non-coding RNAs (lncRNAs) has been increasingly studied recently. In this study, a novel cuproptosis-related lncRNA prognostic signature was developed to investigate biochemical recurrence (BCR) and tumor immune landscape in prostate cancer (PCa).Methods and Materials: The transcriptome data and clinicopathologic information of PCa patients were downloaded from The Cancer Genome Atlas (TCGA). Pearson’s correlation analysis was applied to identify lncRNAs associated with cuproptosis. Based on Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a cuproptosis-related lncRNA prognostic model (risk score) to predict the BCR of PCa patients. Additionally, we also constructed a nomogram with the risk score and clinicopathologic features. The biological function, tumor mutation burden (TMB), immune cell infiltration, expression levels of immune checkpoint genes, and anti-cancer drug sensitivity were investigated.Results: We constructed and validated the cuproptosis-related lncRNA signature prognostic model (risk score) by six crlncRNAs. All patients were divided into the low- and high-risk groups based on the median risk score. The Kaplan–Meier (KM) survival analysis revealed that the high-risk group had shorter BCR-free survival (BCRFS). The risk score has been proven to be an independent prognostic factor of BCR in PCa patients. In addition, a nomogram of risk scores and clinicopathologic features was established and demonstrated an excellent predictive capability of BCR. The ROC curves further validated that this nomogram had higher accuracy of predicting the BCR compared to other clinicopathologic features. We also found that the high-risk group had higher TMB levels and more infiltrated immune cells. Furthermore, patients with high TMB in the high-risk group were inclined to have the shortest BCRFS. Finally, patients in the high-risk group were more susceptible to docetaxel, gefitinib, methotrexate, paclitaxel, and vinblastine.Conclusion: The novel crlncRNA signature prognostic model shows a greatly prognostic prediction value of BCR for PCa patients, extends our thought on the association of cuproptosis and PCa, and provides novel insights into individual-based treatment strategies for PCa.

【 授权许可】

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Copyright © 2023 Ren, Yang, Wang, Lin, Huang, Liu, Pan and Mao.