RNA methylated long non-coding RNAs as potential biomarkers for prognosis prediction in patients with lung adenocarcinoma: development of a risk assessment model

RNA甲基化长链非编码RNA作为肺腺癌患者预后预测的潜在生物标志物:风险评估模型的建立

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作者:Xin Lin #,Jialin Cui #,Yangyang Cheng,Huimin Xu,Wanlin Xie,Jingya Zeng,Yihua Sun

Abstract

Introduction: Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer worldwide. Long non-coding RNA (lncRNAs) are non-protein coding RNAs that are involved in lung cancer. This study aimed to develop a lncRNA-based risk assessment model based on RNA methylation to evaluate the prognosis of patients with LUAD. Method: The TCGA-LUAD dataset consisted of 524 primary tumor samples and 59 normal samples, and the validation set (GSE3121011), which included 246 patients with LUAD, was used for this analysis.Pearson's correlation analysis was used to identify lncRNAs associated with RNA methylation in LUAD. Univariate, least absolute shrinkage and selection operators, and multivariate Cox analyses were used to construct the prognostic model. Gene oncology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to identify enriched biological processes. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to visualize the dataset and gene set variation analyses. Kaplan-Meier and decision curve analyses were used to assess the accuracy. qRT-PCR was used to verify the expression of lncRNAs. Invasion and cell scratch assays were conducted to evaluate migration capacity, and colony formation experiments were performed to assess proliferation ability. Result: Ten RNA methylation-associated lncRNAs were identified to construct risk features. According to the risk model, the patients were categorized into low- and high-risk groups, with the latter exhibiting a less favorable prognosis. The expression levels of the lncRNAs exceeded those in lung epithelial cells. After siRNA transfection, the proliferation and migration abilities of the tumor cells were significantly reduced. The risk-scoring model may be a potential indicator for predicting the sensitivity of patients with LUAD to immunotherapy. Conclusion: The model constructed in this study can accurately predict the prognosis of patients with LUAD, and holds promise for future immunotherapies.

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