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一个新的与铁死亡相关的基因签名,用于预测肺腺癌患者的预后。

A novel ferroptosis-related gene signature for prognostic prediction of patients with lung adenocarcinoma.

机构信息

Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.

China Medical University, Shenyang, China.

出版信息

Aging (Albany NY). 2021 Jun 11;13(12):16144-16164. doi: 10.18632/aging.203140.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is a heterogeneous disease characterized by high mortality and poor prognosis. Ferroptosis, a newly discovered iron-dependent type of cell death, has been found to play a crucial role in the development of cancers. However, little is known about the prognostic value of ferroptosis-related genes (FRGs) in LUAD.

METHODS

In the present study, RNA-seq transcriptome data of LUAD patients were obtained from The Cancer Genome Atlas (TCGA) database. Cox regression analysis was used to construct a multigene signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curves were utilized to assess the prognostic prediction efficiency of the constructed survival model. LUAD patients from the GSE30219 dataset were used for validation.

RESULTS

We found 46 differentially expressed FRGs between LUAD and adjacent normal tissues. Via univariate and multivariate Cox regression analyses, 5 differentially expressed FRGs were identified as being highly correlated with LUAD. Patients were divided into low- and high-risk groups according to the risk score. We found that the overall survival (OS) of patients in the high-risk group was significantly worse than that of their low-risk counterparts. ( < 0.0001 in the TCGA dataset and = 0.044 in the GSE30219 cohort). In addition, gene set variation analysis (GSVA) of the tumor microenvironment of the two groups may explain the different survival of LUAD patients.

CONCLUSIONS

Our study identified a novel FRG signature that could be used to evaluate and predict the prognosis of LUAD patients, which might provide a new therapeutic target for the treatment of LUAD patients.

摘要

背景

肺腺癌 (LUAD) 是一种异质性疾病,其死亡率高,预后差。铁死亡是一种新发现的依赖铁的细胞死亡方式,已被发现在癌症的发展中起着至关重要的作用。然而,关于铁死亡相关基因 (FRGs) 在 LUAD 中的预后价值知之甚少。

方法

本研究从癌症基因组图谱 (TCGA) 数据库中获取 LUAD 患者的 RNA-seq 转录组数据。使用 Cox 回归分析构建多基因特征。 Kaplan-Meier 生存和接收者操作特征 (ROC) 曲线用于评估构建的生存模型的预后预测效率。使用 GSE30219 数据集验证 LUAD 患者。

结果

我们发现 LUAD 与相邻正常组织之间有 46 个差异表达的 FRGs。通过单变量和多变量 Cox 回归分析,确定了 5 个差异表达的 FRGs 与 LUAD 高度相关。根据风险评分将患者分为低风险组和高风险组。我们发现高风险组患者的总生存期 (OS)明显差于低风险组患者。(TCGA 数据集 <0.0001,GSE30219 队列 = 0.044)。此外,两组肿瘤微环境的基因集变异分析 (GSVA) 可能解释了 LUAD 患者不同的生存情况。

结论

我们的研究确定了一个新的 FRG 特征,可以用于评估和预测 LUAD 患者的预后,这可能为 LUAD 患者的治疗提供新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/8266333/48e216c527b4/aging-13-203140-g001.jpg

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