肺腺癌血管生成相关lncRNA预后模型的构建和验证。
Construction and validation of an angiogenesis-related lncRNA prognostic model in lung adenocarcinoma.
发表日期:2023
作者:
Quan Gong, Xianda Huang, Xiaobo Chen, Lijuan Zhang, Chunyan Zhou, Shijuan Li, Tingting Song, Li Zhuang
来源:
Frontiers in Genetics
摘要:
背景:越来越多的证据表明,长非编码RNA(lncRNA)可以作为癌症潜在的预后因子。本研究旨在使用与血管生成相关的长非编码RNA(lncRNA)作为潜在预后因子来开发肺腺癌(LUAD)的预后模型。 方法:分析The Cancer Genome Atlas(TCGA)和Gene Expression Omnibus(GEO)中的转录组数据,以确定在LUAD中异常表达的与血管生成相关的lncRNA。使用差异表达分析、重叠分析、Pearson相关分析和Cox回归分析构建了一个预后签名。使用K-M和ROC曲线评估模型的有效性,并在GSE30219数据集中进行独立外部验证。确定了预后性lncRNA-microRNA(miRNA)-信使RNA(mRNA)竞争性内源性RNA(ceRNA)网络。还分析了免疫细胞浸润和突变特征。使用定量实时PCR(qRT-PCR)基因芯片定量了四个人类血管生成相关的lncRNA的表达。 结果:在LUAD中确定了26个异常表达的与血管生成相关的lncRNA,并构建了一个基于LINC00857、RBPMS-AS1、SYNPR-AS1和LINC00460的Cox风险模型,这可能是LUAD的独立预后预测因子。低风险组具有显着更好的预后,并且与更高丰度的休息免疫细胞和较低的免疫检查点分子表达相关。此外,基于这四个预后性lncRNA预测了105种ceRNA机制。 qRT-PCR结果显示,LINC00857、SYNPR-AS1和LINC00460在肿瘤组织中显著高表达,而RBPMS-AS1在癌旁组织中高表达。 结论:本研究确定的四个血管生成相关的lncRNA可能作为LUAD患者的有前途的预后生物标志物。 版权所有 ©2023 Gong,Huang,Chen,Zhang,Zhou,Li,Song和Zhuang。
Background: There is increasing evidence that long non-coding RNAs (lncRNAs) can be used as potential prognostic factors for cancer. This study aimed to develop a prognostic model for lung adenocarcinoma (LUAD) using angiogenesis-related long non-coding RNAs (lncRNAs) as potential prognostic factors. Methods: Transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify aberrantly expressed angiogenesis-related lncRNAs in LUAD. A prognostic signature was constructed using differential expression analysis, overlap analysis, Pearson correlation analysis, and Cox regression analysis. The model's validity was assessed using K-M and ROC curves, and independent external validation was performed in the GSE30219 dataset. Prognostic lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks were identified. Immune cell infiltration and mutational characteristics were also analyzed. The expression of four human angiogenesis-associated lncRNAs was quantified using quantitative real-time PCR (qRT-PCR) gene arrays. Results: A total of 26 aberrantly expressed angiogenesis-related lncRNAs in LUAD were identified, and a Cox risk model based on LINC00857, RBPMS-AS1, SYNPR-AS1, and LINC00460 was constructed, which may be an independent prognostic predictor for LUAD. The low-risk group had a significant better prognosis and was associated with a higher abundance of resting immune cells and a lower expression of immune checkpoint molecules. Moreover, 105 ceRNA mechanisms were predicted based on the four prognostic lncRNAs. qRT-PCR results showed that LINC00857, SYNPR-AS1, and LINC00460 were significantly highly expressed in tumor tissues, while RBPMS-AS1 was highly expressed in paracancerous tissues. Conclusion: The four angiogenesis-related lncRNAs identified in this study could serve as a promising prognostic biomarker for LUAD patients.Copyright © 2023 Gong, Huang, Chen, Zhang, Zhou, Li, Song and Zhuang.