Lu Lu, Liu Le-Ping, Zhao Qiang-Qiang, Gui Rong, Zhao Qin-Yu
Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China.
College of Engineering and Computer Science, Australian National University, Canberra, ACT, Australia.
Front Oncol. 2021 Jun 23;11:675545. doi: 10.3389/fonc.2021.675545. eCollection 2021.
Lung adenocarcinoma (LUAD) is a highly heterogeneous malignancy, which makes prognosis prediction of LUAD very challenging. Ferroptosis is an iron-dependent cell death mechanism that is important in the survival of tumor cells. Long non-coding RNAs (lncRNAs) are considered to be key regulators of LUAD development and are involved in ferroptosis of tumor cells, and ferroptosis-related lncRNAs have gradually emerged as new targets for LUAD treatment and prognosis. It is essential to determine the prognostic value of ferroptosis-related lncRNAs in LUAD. In this study, we obtained RNA sequencing (RNA-seq) data and corresponding clinical information of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and ferroptosis-related lncRNAs by co-expression analysis. The best predictors associated with LUAD prognosis, including C5orf64, LINC01800, LINC00968, LINC01352, PGM5-AS1, LINC02097, DEPDC1-AS1, WWC2-AS2, SATB2-AS1, LINC00628, LINC01537, LMO7DN, were identified by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, and the LUAD risk prediction model was successfully constructed. Kaplan-Meier analysis, receiver operating characteristic (ROC) time curve analysis and univariate and multivariate Cox regression analysis and further demonstrated that the model has excellent robustness and predictive ability. Further, based on the risk prediction model, functional enrichment analysis revealed that 12 prognostic indicators involved a variety of cellular functions and signaling pathways, and the immune status was different in the high-risk and low-risk groups. In conclusion, a risk model of 12 ferroptosis related lncRNAs has important prognostic value for LUAD and may be ferroptosis-related therapeutic targets in the clinic.
肺腺癌(LUAD)是一种高度异质性的恶性肿瘤,这使得LUAD的预后预测极具挑战性。铁死亡是一种铁依赖性细胞死亡机制,对肿瘤细胞的存活至关重要。长链非编码RNA(lncRNAs)被认为是LUAD发展的关键调节因子,并参与肿瘤细胞的铁死亡,与铁死亡相关的lncRNAs已逐渐成为LUAD治疗和预后的新靶点。确定与铁死亡相关的lncRNAs在LUAD中的预后价值至关重要。在本研究中,我们从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中获取了LUAD患者的RNA测序(RNA-seq)数据及相应临床信息,并通过共表达分析得到了与铁死亡相关的lncRNAs。通过最小绝对收缩和选择算子(LASSO)Cox回归分析确定了与LUAD预后相关的最佳预测指标,包括C5orf64、LINC01800、LINC00968、LINC01352、PGM5-AS1、LINC02097、DEPDC1-AS1、WWC2-AS2、SATB2-AS1、LINC00628、LINC01537、LMO7DN,并成功构建了LUAD风险预测模型。Kaplan-Meier分析、受试者工作特征(ROC)时间曲线分析以及单因素和多因素Cox回归分析进一步证明该模型具有出色的稳健性和预测能力。此外,基于风险预测模型的功能富集分析表明,12个预后指标涉及多种细胞功能和信号通路,高危组和低危组的免疫状态不同。总之,一个由12个与铁死亡相关的lncRNAs组成的风险模型对LUAD具有重要的预后价值,可能是临床上与铁死亡相关的治疗靶点。
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