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肺腺癌中铁死亡相关长链非编码RNA的预后标志物

Prognostic markers of ferroptosis-related long non-coding RNA in lung adenocarcinomas.

作者信息

Mao Kaimin, Tang Ri, Wu Yali, Zhang Zhiyun, Gao Yuan, Huang Huijing

机构信息

Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Genet. 2023 Feb 27;14:1118273. doi: 10.3389/fgene.2023.1118273. eCollection 2023.

Abstract

Ferroptosis is a recently established type of iron-dependent programmed cell death. Growing studies have focused on the function of ferroptosis in cancers, including lung adenocarcinoma (LUAD). However, the factors involved in the regulation of ferroptosis-related genes are not fully understood. In this study, we collected data from lung adenocarcinoma datasets of the Cancer Genome Atlas (TCGA-LUAD). The expression profiles of 60 ferroptosis-related genes were screened, and two differentially expressed ferroptosis subtypes were identified. We found the two ferroptosis subtypes can predict clinical outcomes and therapeutic responses in LUAD patients. Furthermore, key long non-coding RNAs (lncRNAs) were screened by single factor Cox and least absolute shrinkage and selection operator (LASSO) based on which co-expressed with the 60 ferroptosis-related genes. We then established a risk score model which included 13 LUAD ferroptosis-related lncRNAs with a multi-factor Cox regression. The risk score model showed a good performance in evaluating the outcome of LUAD. What's more, we divided TCGA-LUAD tumor samples into two groups with high- and low-risk scores and further explored the differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration among different LUAD tumor risk score groups and evaluate the predictive ability of risk score for immunotherapy benefit. Our findings provide good support for immunotherapy in LUAD in the future.

摘要

铁死亡是一种最近确定的铁依赖性程序性细胞死亡类型。越来越多的研究聚焦于铁死亡在癌症中的作用,包括肺腺癌(LUAD)。然而,铁死亡相关基因调控所涉及的因素尚未完全明确。在本研究中,我们从癌症基因组图谱(TCGA-LUAD)的肺腺癌数据集中收集数据。筛选了60个铁死亡相关基因的表达谱,并鉴定出两种差异表达的铁死亡亚型。我们发现这两种铁死亡亚型可以预测LUAD患者的临床结局和治疗反应。此外,基于单因素Cox分析和最小绝对收缩和选择算子(LASSO)筛选出关键的长链非编码RNA(lncRNA),这些lncRNA与60个铁死亡相关基因共表达。然后,我们通过多因素Cox回归建立了一个包含13个与LUAD铁死亡相关lncRNA的风险评分模型。该风险评分模型在评估LUAD结局方面表现良好。此外,我们将TCGA-LUAD肿瘤样本分为高风险和低风险评分两组,并进一步探讨不同LUAD肿瘤风险评分组之间临床特征、肿瘤突变负担和肿瘤免疫细胞浸润的差异,评估风险评分对免疫治疗获益的预测能力。我们的研究结果为未来LUAD的免疫治疗提供了有力支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e87/10009162/725d84d12fb8/fgene-14-1118273-g001.jpg

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