Table_1_Identification of a Ferroptosis-Related LncRNA Signature as a Novel Prognosis Model for Lung Adenocarcinoma.xlsx

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（Lung adenocarcinoma, 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（Ferroptosis）是一种铁依赖性细胞死亡机制，在肿瘤细胞存活过程中发挥重要作用。长链非编码RNA（Long non-coding RNAs, lncRNAs）被认为是LUAD发生发展的关键调控因子，且参与肿瘤细胞的铁死亡过程，与铁死亡相关的lncRNAs也逐渐成为LUAD治疗与预后研究的新型靶点。明确铁死亡相关lncRNAs在LUAD中的预后价值至关重要。本研究从癌症基因组图谱（The Cancer Genome Atlas, TCGA）与基因表达综合数据库（Gene Expression Omnibus, GEO）中获取LUAD患者的RNA测序（RNA sequencing, RNA-seq）数据及对应临床信息，并通过共表达分析筛选出铁死亡相关lncRNAs。随后通过最小绝对收缩与选择算子（Least Absolute Shrinkage and Selection Operator, LASSO）Cox回归分析，筛选出与LUAD预后相关的最优预测因子，包括C5orf64、LINC01800、LINC00968、LINC01352、PGM5-AS1、LINC02097、DEPDC1-AS1、WWC2-AS2、SATB2-AS1、LINC00628、LINC01537、LMO7DN，并成功构建LUAD风险预测模型。经Kaplan-Meier分析、受试者工作特征（Receiver Operating Characteristic, ROC）时间曲线分析、单因素及多因素Cox回归分析验证，该模型展现出优异的稳健性与预测能力。进一步基于该风险预测模型开展功能富集分析，结果显示12个预后指标涉及多种细胞功能与信号通路，且高危组与低危组的免疫状态存在显著差异。综上，本研究构建的12个铁死亡相关lncRNAs风险模型对LUAD具有重要的预后价值，有望成为临床中与铁死亡相关的治疗靶点。