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基于三种分子亚型解析糖酵解相关 lncRNAs 在肺腺癌中关键作用。

Understanding the Critical Role of Glycolysis-Related lncRNAs in Lung Adenocarcinoma Based on Three Molecular Subtypes.

机构信息

Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 43000 Hubei Province, China.

Department of Clinical Translational Medicine, Yucebio Biotechnology Co., Ltd, Yantian District, Shenzhen, Guangdong Province, 4th Floor, Phase I, Dabaihui Center, No. 2002, Shenyan Road, Haishan Street, Yantian District, Shenzhen, China.

出版信息

Biomed Res Int. 2022 Feb 7;2022:7587398. doi: 10.1155/2022/7587398. eCollection 2022.

DOI:10.1155/2022/7587398
PMID:35178454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8845143/
Abstract

BACKGROUND

Glycolysis is closely associated with tumor progression, but the roles of lncRNAs in glycolysis have not been comprehensively investigated in lung adenocarcinoma (LUAD). This study is aimed at studying the possible mechanisms of glycolysis-related lncRNAs in tumor development and providing a guidance for targeted therapy.

METHODS

Unsupervised consensus clustering was used to identify molecular subtypes. Gene enrichment analysis was applied to screen important pathways involved in tumor progression. A series of immune analysis was performed to assess immune infiltration. Critical transcription factors (TFs) interacting with lncRNAs were selected by Pearson correlation analysis. A first-order partial correlation analysis was implemented to identify critical lncRNAs with prognostic significance.

RESULTS

Three molecular subtypes (C1, C2, and C3) were identified with distinct overall survival. Three subtypes showed differential immune infiltration, and C3 subtype was the optimal for immunotherapy treatment. Ten lncRNA-TF pairs among four glycolysis-related lncRNAs (FTX, LINC00472, PSMA3-AS1, and SNHG14) and six TFs (FOXP1, SP1, MYC, FOXM1, HIF1A, and FOS) were involved in tumor progression. We identified four critical glycolysis-related lncRNAs significantly associated with prognosis.

CONCLUSIONS

This study identified three molecular subtypes that could guide personalized therapy. The four-lncRNA prognostic model can serve as an indicator for predicting prognosis or early screening of lung adenocarcinoma patients. The current results improve the understanding of the relation between lncRNAs and glycolysis.

摘要

背景

糖酵解与肿瘤进展密切相关,但长链非编码 RNA(lncRNA)在肺腺癌(LUAD)中的糖酵解作用尚未得到全面研究。本研究旨在研究糖酵解相关 lncRNA 在肿瘤发展中的可能机制,并为靶向治疗提供指导。

方法

采用无监督共识聚类法识别分子亚型。采用基因富集分析筛选肿瘤进展相关重要通路。进行一系列免疫分析以评估免疫浸润。通过 Pearson 相关分析选择与 lncRNA 相互作用的关键转录因子(TF)。采用一阶偏相关分析鉴定具有预后意义的关键 lncRNA。

结果

鉴定出具有不同总生存期的三个分子亚型(C1、C2 和 C3)。三种亚型表现出不同的免疫浸润,C3 亚型是免疫治疗的最佳选择。四个糖酵解相关 lncRNA(FTX、LINC00472、PSMA3-AS1 和 SNHG14)和六个 TF(FOXP1、SP1、MYC、FOXM1、HIF1A 和 FOS)中的 10 个 lncRNA-TF 对参与肿瘤进展。我们确定了四个与预后显著相关的关键糖酵解相关 lncRNA。

结论

本研究鉴定了三个可能指导个体化治疗的分子亚型。四-lncRNA 预后模型可作为预测肺腺癌患者预后或早期筛查的指标。目前的结果提高了对 lncRNA 与糖酵解之间关系的理解。

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