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肺腺癌中铁死亡相关长链非编码RNA预后特征及竞争性内源性RNA网络的构建

Construction of a Ferroptosis-Related Long Non-coding RNA Prognostic Signature and Competing Endogenous RNA Network in Lung Adenocarcinoma.

作者信息

Fei Xiang, Hu Congli, Wang Xinyu, Lu Chaojing, Chen Hezhong, Sun Bin, Li Chunguang

机构信息

Department of Thoracic Surgery, Changhai Hospital, Navy Military Medical University, Shanghai, China.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

出版信息

Front Cell Dev Biol. 2021 Nov 8;9:751490. doi: 10.3389/fcell.2021.751490. eCollection 2021.

Abstract

Ferroptosis-related genes play an important role in the progression of lung adenocarcinoma (LUAD). However, the potential function of ferroptosis-related lncRNAs in LUAD has not been fully elucidated. Thus, to explore the potential role of ferroptosis-related lncRNAs in LUAD, the transcriptome RNA-seq data and corresponding clinical data of LUAD were downloaded from the TCGA dataset. Pearson correlation was used to mine ferroptosis-related lncRNAs. Differential expression and univariate Cox analysis were performed to screen prognosis related lncRNAs. A ferroptosis-related lncRNA prognostic signature (FLPS), which included six ferroptosis-related lncRNAs, was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were divided into a high risk-score group and low risk-score group by the median risk score. Receiver operating characteristic (ROC) curves, principal component analysis (PCA), and univariate and multivariate Cox regression were performed to confirm the validity of FLPS. Enrichment analysis showed that the biological processes, pathways and markers associated with malignant tumors were more common in high-risk subgroups. There were significant differences in immune microenvironment and immune cells between high- and low-risk groups. Then, a nomogram was constructed. We further investigated the relationship between six ferroptosis-related lncRNAs and tumor microenvironment and tumor stemness. A competing endogenous RNA (ceRNA) network was established based on the six ferroptosis-related lncRNAs. Finally, we detected the expression levels of ferroptosis-related lncRNAs in clinical samples through quantitative real-time polymerase chain reaction assay (qRT-PCR). In conclusion, we identified the prognostic ferroptosis-related lncRNAs in LUAD and constructed a prognostic signature which provided a new strategy for the evaluation and prediction of prognosis in LUAD.

摘要

铁死亡相关基因在肺腺癌(LUAD)进展中起重要作用。然而,铁死亡相关长链非编码RNA(lncRNA)在LUAD中的潜在功能尚未完全阐明。因此,为了探索铁死亡相关lncRNA在LUAD中的潜在作用,从TCGA数据集中下载了LUAD的转录组RNA测序数据及相应临床数据。采用Pearson相关性分析挖掘铁死亡相关lncRNA。进行差异表达分析和单因素Cox分析以筛选与预后相关的lncRNA。通过最小绝对收缩和选择算子(LASSO)Cox回归构建了包含6个铁死亡相关lncRNA的铁死亡相关lncRNA预后特征(FLPS)。根据中位风险评分将患者分为高风险评分组和低风险评分组。绘制受试者工作特征(ROC)曲线、主成分分析(PCA)以及进行单因素和多因素Cox回归以证实FLPS的有效性。富集分析表明,与恶性肿瘤相关的生物学过程、通路和标志物在高风险亚组中更为常见。高风险组和低风险组之间的免疫微环境和免疫细胞存在显著差异。然后,构建了列线图。我们进一步研究了6个铁死亡相关lncRNA与肿瘤微环境和肿瘤干性之间的关系。基于这6个铁死亡相关lncRNA建立了竞争性内源性RNA(ceRNA)网络。最后,通过定量实时聚合酶链反应分析(qRT-PCR)检测临床样本中铁死亡相关lncRNA的表达水平。总之,我们鉴定了LUAD中与预后相关的铁死亡相关lncRNA并构建了预后特征,为LUAD预后的评估和预测提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f79c/8606539/27ec93a28ef9/fcell-09-751490-g001.jpg

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