研究动态
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Cuprotosis 相关 lncRNA 预测 LUAD 的预后和免疫反应。

Cuproptosis-Related lncRNA Predict Prognosis and Immune Response of LUAD.

发表日期:2024
作者: Qianhui Zhou, Yi Liu, Yan Gao, Lingli Quan, Lin Wang, Hao Wang
来源: Cell Death & Disease

摘要:

肺癌是全球癌症死亡的主要原因,主要是由于肺腺癌(LUAD)。然而,程序性细胞死亡的异质性导致不同的预后和预测结果。本研究旨在开发基于铜凋亡相关lncRNA的LUAD评估标志物。首先,从癌症基因组图谱(TCGA)下载与LUAD相关的转录组数据和临床数据,并分析铜凋亡相关基因,以确定铜凋亡相关lncRNA 。进行单变量、LASSO 和多变量 Cox 回归分析来构建铜凋亡相关的 lncRNA 模型。使用预后风险值将 LUAD 患者分为高风险组和低风险组。采用Kaplan-Meier分析、PCA、GSEA和列线图来评估和验证结果。鉴定出7个与铜凋亡相关的lncRNA,并创建了风险模型。高危肿瘤中95.54%的病例出现铜凋亡相关基因改变,而低危肿瘤中85.65%的病例出现铜凋亡相关基因改变,主要涉及TP53。作为 1 年、3 年和 5 年总生存率的预测因子,风险值优于其他临床变量和肿瘤突变负荷。基于铜凋亡相关 lncRNA 的风险模型证明了 LUAD 评估的高度有效性,可能影响个体化治疗方法。对 LUAD 组织和邻近正常组织中四种候选铜凋亡相关 lncRNA(AL606834.1、AL161431.1、AC007613.1 和 LINC02835)的表达分析显示 AL606834.1 和 AL161431.1 在 LUAD 组织中的表达水平显着较高,阳性与肿瘤分期、淋巴结转移和组织病理学分级相关。相反,AC007613.1 和 LINC02835 表现出较低的表达水平,与这些因素呈负相关。 AL606834.1和AL161431.1的高表达表明预后不良,而AC007613.1和LINC02835的低表达与不良结果相关。单变量和多变量分析证实这些lncRNA是LUAD预后的独立危险因素。4个与铜凋亡相关的lncRNA(lncRNAsAL606834.1、AL161431.1、AC007613.1和LINC02835)可以准确预测LUAD患者的预后,并可能提供新的见解。进入临床应用和免疫治疗。© 2024 Zhou et al.
Lung cancer is the leading cause of cancer deaths worldwide, primarily due to lung adenocarcinoma (LUAD). However, the heterogeneity of programmed cell death results in varied prognostic and predictive outcomes. This study aimed to develop an LUAD evaluation marker based on cuproptosis-related lncRNAs.First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate, LASSO, and multivariate Cox regression analyses were conducted to construct cuproptosis-associated lncRNA models. LUAD patients were categorized into high-risk and low-risk groups using prognostic risk values. Kaplan-Meier analysis, PCA, GSEA, and nomograms were employed to evaluate and validate the results.7 cuproptosis-related lncRNAs were identified, and a risk model was created. High-risk tumors exhibited cuproptosis-related gene alterations in 95.54% of cases, while low-risk tumors showed alterations in 85.65% of cases, mainly involving TP53. The risk value outperformed other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival. The cuproptosis-related lncRNA-based risk model demonstrated high validity for LUAD evaluation, potentially influencing individualized treatment approaches. Expression analysis of four candidate cuproptosis-related lncRNAs (AL606834.1, AL161431.1, AC007613.1, and LINC02835) in LUAD tissues and adjacent normal tissues revealed significantly higher expression levels of AL606834.1 and AL161431.1 in LUAD tissues, positively correlating with tumor stage, lymph node metastasis, and histopathological grade. Conversely, AC007613.1 and LINC02835 exhibited lower expression levels, negatively correlating with these factors. High expression of AL606834.1 and AL161431.1 indicated poor prognosis, while low expression of AC007613.1 and LINC02835 was associated with unfavorable outcomes. Univariate and multivariate analyses confirmed these lncRNAs as independent risk factors for LUAD prognosis.The 4 cuproptosis-related (lncRNAsAL606834.1, AL161431.1, AC007613.1, and LINC02835) can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.© 2024 Zhou et al.