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建立和验证与铜死亡相关的 lncRNA 特征,用于预测肝细胞癌的预后和潜在的靶向治疗。

Establishment and validation of a cuproptosis-related lncRNA signature that predicts prognosis and potential targeted therapy in hepatocellular carcinoma.

机构信息

Gastroenterology Department, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

Key Laboratory of Jiangxi Province for Transfusion Medicine, First Affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

Biotechnol Genet Eng Rev. 2024 Oct;40(2):739-764. doi: 10.1080/02648725.2023.2190640. Epub 2023 Mar 23.

Abstract

BACKGROUND

Cuproptosis is a recently identified form of programmed cell death and could be a new direction for tumour therapy, and it has important clinical implications. Long non-coding RNAs (lncRNAs) can intervene in diverse biological processes and have a decisive role in hepatocellular carcinoma (HCC). However, how cuproptosis-related lncRNAs (CRLs) participate in regulating HCC has yet to be recognised. This study aimed to establish and validate a prognostic signature of CRLs and to analyse their clinical value in HCC patients.

METHODS

To analyse the function of CRLs in the prognosis of HCC, RNA sequencing data, mutation data, and clinically relevant data were collected from the Cancer Genome Atlas Database (TCGA). Then, TCGA cohort was randomly divided into training and test sets. The training set was utilized to define prognostic signature of CRLs using bioinformatics methods. Subsequently, we verified the accuracy of this prognostic signature in the test set. Finally, we performed immune-related analysis, the half-maximal inhibitory concentration (IC50) prediction, gene set enrichment analysis, and tumour mutational burden (TMB) analysis.

RESULTS

We established a prognostic signature for the CRLs (SNHG4, AC026412.3, AL590705.3, and CDKN2A-DT). This signature-based risk group displayed an accurate predictive ability for the survival time of patients with HCC. We observed discrepancies in immune cells, immune function, the expression level of genes related to immune checkpoints, and TMB in high- and low-risk groups.

CONCLUSION

This CRLs prognostic signature could predict clinical outcomes in patients with HCC as well as the efficacy of targeted and therapy immunotherapy.

摘要

背景

铜死亡是一种新发现的细胞程序性死亡形式,可能成为肿瘤治疗的新方向,具有重要的临床意义。长链非编码 RNA(lncRNA)可以干预多种生物过程,并在肝细胞癌(HCC)中起决定性作用。然而,铜死亡相关 lncRNA(CRL)如何参与调节 HCC 尚未得到认识。本研究旨在建立和验证 CRL 的预后签名,并分析其在 HCC 患者中的临床价值。

方法

为了分析 CRL 在 HCC 预后中的作用,从癌症基因组图谱数据库(TCGA)收集了 RNA 测序数据、突变数据和临床相关数据。然后,TCGA 队列被随机分为训练集和测试集。使用生物信息学方法,利用训练集定义 CRL 的预后签名。随后,我们在测试集中验证了该预后签名的准确性。最后,我们进行了免疫相关分析、半最大抑制浓度(IC50)预测、基因集富集分析和肿瘤突变负荷(TMB)分析。

结果

我们建立了一个 CRL 的预后签名(SNHG4、AC026412.3、AL590705.3 和 CDKN2A-DT)。该基于签名的风险组能够准确预测 HCC 患者的生存时间。我们观察到高风险组和低风险组之间免疫细胞、免疫功能、免疫检查点相关基因的表达水平以及 TMB 存在差异。

结论

该 CRL 预后签名可以预测 HCC 患者的临床结局以及靶向和免疫治疗的疗效。

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