利用癌症基因组图谱中基于铁死亡相关长链非编码RNA对胰腺癌进行预后评估

Prognostication of Pancreatic Cancer Using The Cancer Genome Atlas Based Ferroptosis-Related Long Non-Coding RNAs.

作者信息

Li Jiayu, Zhang Jinghui, Tao Shuiliang, Hong Jiaze, Zhang Yuyan, Chen Weiyan

机构信息

The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.

School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Front Genet. 2022 Feb 14;13:838021. doi: 10.3389/fgene.2022.838021. eCollection 2022.

Abstract

Long non-coding RNAs (lncRNAs) are key regulators of pancreatic cancer development and are involved in ferroptosis regulation. LncRNA transcript levels serve as a prognostic factor for pancreatic cancer. Therefore, identifying ferroptosis-related lncRNAs (FRLs) with prognostic value in pancreatic cancer is critical. In this study, FRLs were identified by combining The Cancer Genome Atlas (TCGA) and FerrDb databases. For training cohort, univariate Cox, Lasso, and multivariate Cox regression analyses were applied to identify prognosis FRLs and then construct a prognostic FRLs signature. Testing cohort and entire cohort were applied to validate the prognostic signature. Moreover, the nomogram was performed to predict prognosis at different clinicopathological stages and risk scores. A co-expression network with 76 lncRNA-mRNA targets was constructed. Univariate Cox analysis was performed to analyze the prognostic value of 193 lncRNAs. Furthermore, the least absolute shrinkage and selection operator and the multivariate Cox analysis were used to assess the prognostic value of these ferroptosis-related lncRNAs. A prognostic risk model, of six lncRNAs, including LINC01705, AC068620.2, TRAF3IP2-AS1, AC092171.2, AC099850.3, and MIR193BHG was constructed. The Kaplan Meier (KM) and time-related receiver operating characteristic (ROC) curve analysis were performed to calculate overall survival and compare high- and low-risk groups. There was also a significant difference in survival time between the high-risk and low-risk groups for the testing cohort and the entire cohort, with AUCs of .723, .753, respectively. Combined with clinicopathological characteristics, the risk model was validated as a new independent prognostic factor for pancreatic adenocarcinoma through univariate and multivariate Cox regression. Moreover, a nomogram showed good prediction. The signature of six FRLs had significant prognostic value for pancreatic adenocarcinoma. They may be a promising therapeutic target in clinical practice.

摘要

长链非编码RNA(lncRNAs)是胰腺癌发展的关键调节因子,并参与铁死亡调节。lncRNA转录水平是胰腺癌的一个预后因素。因此,识别在胰腺癌中具有预后价值的铁死亡相关lncRNAs(FRLs)至关重要。在本研究中,通过整合癌症基因组图谱(TCGA)和FerrDb数据库来识别FRLs。对于训练队列,应用单变量Cox、Lasso和多变量Cox回归分析来识别预后FRLs,然后构建一个预后FRLs特征。测试队列和整个队列用于验证该预后特征。此外,还制作了列线图以预测不同临床病理阶段和风险评分的预后。构建了一个包含76个lncRNA - mRNA靶点的共表达网络。进行单变量Cox分析以分析193个lncRNAs的预后价值。此外,使用最小绝对收缩和选择算子以及多变量Cox分析来评估这些铁死亡相关lncRNAs的预后价值。构建了一个由六个lncRNAs组成的预后风险模型,包括LINC01705、AC068620.2、TRAF3IP2 - AS1、AC092171.2、AC099850.3和MIR193BHG。进行Kaplan - Meier(KM)和时间相关的受试者工作特征(ROC)曲线分析以计算总生存期并比较高风险和低风险组。测试队列和整个队列的高风险组和低风险组之间的生存时间也存在显著差异,AUC分别为0.723和0.753。结合临床病理特征,通过单变量和多变量Cox回归验证该风险模型是胰腺腺癌的一个新的独立预后因素。此外,列线图显示出良好的预测效果。六个FRLs的特征对胰腺腺癌具有显著的预后价值。它们可能是临床实践中一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/8883032/1724c4a58f42/fgene-13-838021-g001.jpg

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