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铜死亡相关 lncRNA 特征作为弥漫性大 B 细胞淋巴瘤的预后工具和治疗靶点。

Cuproptosis-related lncRNA signature as a prognostic tool and therapeutic target in diffuse large B cell lymphoma.

机构信息

Department of Hematology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.

Department of Lymphoma and Plasmacytoma Disease, Senior Department of Hematology, The Fifth Medical Center of PLA General Hospital, Beijing, China.

出版信息

Sci Rep. 2024 Jun 5;14(1):12926. doi: 10.1038/s41598-024-63433-w.


DOI:10.1038/s41598-024-63433-w
PMID:38839842
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11153514/
Abstract

Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein-protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.

摘要

铜死亡是一种依赖于线粒体呼吸的新定义的细胞死亡形式。长链非编码 RNA(lncRNA)在肿瘤发生和转移中发挥着关键作用。然而,铜死亡相关 lncRNA 是否参与弥漫性大 B 细胞淋巴瘤(DLBCL)的发病机制尚不清楚。本研究旨在鉴定 DLBCL 中与铜死亡相关的 lncRNA 的预后特征,并研究其潜在的分子功能。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中收集了用于 DLBCL 的 RNA-Seq 数据和临床信息。通过 Pearson 相关分析筛选出铜死亡相关 lncRNA。利用单因素 Cox、最小绝对值收缩和选择算子(Lasso)和多因素 Cox 回归分析,我们鉴定出 7 个铜死亡相关 lncRNA,并开发了一个风险预测模型,以评估其在多个组中的预后价值。GO 和 KEGG 功能分析、单样本 GSEA(ssGSEA)和 ESTIMATE 算法用于分析不同风险组之间的机制和免疫状态。此外,药物敏感性分析确定了对 DLBCL 有潜在疗效的药物。最后,基于加权基因共表达网络分析(WGCNA)构建蛋白质-蛋白质相互作用(PPI)网络。我们鉴定了一组 7 个铜死亡相关 lncRNA,包括 LINC00294、RNF139-AS1、LINC00654、WWC2-AS2、LINC00661、LINC01165 和 LINC01398,基于这些 lncRNA 构建了 DLBCL 的风险模型。与低风险组相比,高风险组的生存时间更短,基于signature 的风险评分在预测 DLBCL 患者预后方面优于传统临床特征。通过分析两组之间的免疫景观,我们发现高危 DLBCL 组中免疫抑制性细胞类型显著增加。此外,功能富集分析突出了差异表达基因与代谢、炎症和免疫相关途径的关联。我们还发现,高危组对长春瑞滨和乙胺嘧啶更敏感。建立了一个铜死亡相关 lncRNA 特征来预测预后,并为 DLBCL 患者提供潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/314837538a2e/41598_2024_63433_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/f4af7cbd0425/41598_2024_63433_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/314837538a2e/41598_2024_63433_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/f58aac3522cb/41598_2024_63433_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/046a60ac94f0/41598_2024_63433_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/efb434841f5a/41598_2024_63433_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/6ded81c8fb1d/41598_2024_63433_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/1bb7e350e290/41598_2024_63433_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/dbbd96f3a87b/41598_2024_63433_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/c4b6d2f35d54/41598_2024_63433_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/f4af7cbd0425/41598_2024_63433_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0315/11153514/314837538a2e/41598_2024_63433_Fig9_HTML.jpg

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引用本文的文献

[1]
Cuproptosis: A Review on Mechanisms, Role in Solid and Hematological Tumors, and Association with Viral Infections.

Mediterr J Hematol Infect Dis. 2025-7-1

[2]
Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system.

Cancer Pathog Ther. 2024-7-27

[3]
Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.

Int J Mol Sci. 2024-10-23

[4]
Comprehensive single-cell and bulk transcriptomic analyses to develop an NK cell-derived gene signature for prognostic assessment and precision medicine in breast cancer.

Front Immunol. 2024

[5]
lncRNAs as prognostic markers and therapeutic targets in cuproptosis-mediated cancer.

Clin Exp Med. 2024-9-26

本文引用的文献

[1]
LncRNAs and regulated cell death in tumor cells.

Front Oncol. 2023-5-29

[2]
Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD-L1 for Enhanced Cancer Immunotherapy.

Adv Mater. 2023-6

[3]
Development and validation of a cuproptosis-associated prognostic model for diffuse large B-cell lymphoma.

Front Oncol. 2023-1-12

[4]
Advanced Ann Arbor stage and age over 60 years as prognostic predictors in patients with primary cervical lymphoma: a retrospective cohort study and systematic review.

BMC Cancer. 2023-1-27

[5]
Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients, with Diffuse Large B-Cell Lymphoma.

J Clin Med. 2022-12-1

[6]
A novel cuproptosis-related lncRNA signature predicts the prognosis and immune landscape in bladder cancer.

Front Immunol. 2022

[7]
Database Mining Detected a Cuproptosis-Related Prognostic Signature and a Related Regulatory Axis in Breast Cancer.

Dis Markers. 2022

[8]
An Enzyme-Engineered Nonporous Copper(I) Coordination Polymer Nanoplatform for Cuproptosis-Based Synergistic Cancer Therapy.

Adv Mater. 2022-10

[9]
Clinical significance of circulating neutrophils and lymphocyte subsets in newly diagnosed patients with diffuse large B-cell lymphoma.

Clin Exp Med. 2023-7

[10]
A novel cuproptosis-related prognostic lncRNA signature and lncRNA MIR31HG/miR-193a-3p/TNFRSF21 regulatory axis in lung adenocarcinoma.

Front Oncol. 2022-7-22

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