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基于免疫相关长链非编码RNA整合多种机器学习算法用于胃癌预后预测

Integrating multiple machine learning algorithms for prognostic prediction of gastric cancer based on immune-related lncRNAs.

作者信息

Li Guoqi, Huo Diwei, Guo Naifu, Li Yi, Ma Hongzhe, Liu Lei, Xie Hongbo, Zhang Denan, Qu Bo, Chen Xiujie

机构信息

Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Genet. 2023 Apr 4;14:1106724. doi: 10.3389/fgene.2023.1106724. eCollection 2023.

Abstract

Long non-coding RNAs (lncRNAs) play an important role in the immune regulation of gastric cancer (GC). However, the clinical application value of immune-related lncRNAs has not been fully developed. It is of great significance to overcome the challenges of prognostic prediction and classification of gastric cancer patients based on the current study. In this study, the R package ImmLnc was used to obtain immune-related lncRNAs of The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) project, and univariate Cox regression analysis was performed to find prognostic immune-related lncRNAs. A total of 117 combinations based on 10 algorithms were integrated to determine the immune-related lncRNA prognostic model (ILPM). According to the ILPM, the least absolute shrinkage and selection operator (LASSO) regression was employed to find the major lncRNAs and develop the risk model. ssGSEA, CIBERSORT algorithm, the R package maftools, pRRophetic, and clusterProfiler were employed for measuring the proportion of immune cells among risk groups, genomic mutation difference, drug sensitivity analysis, and pathway enrichment score. A total of 321 immune-related lncRNAs were found, and there were 26 prognostic immune-related lncRNAs. According to the ILPM, 18 of 26 lncRNAs were selected and the risk score (RS) developed by the 18-lncRNA signature had good strength in the TCGA training set and Gene Expression Omnibus (GEO) validation datasets. Patients were divided into high- and low-risk groups according to the median RS, and the low-risk group had a better prognosis, tumor immune microenvironment, and tumor signature enrichment score and a higher metabolism, frequency of genomic mutations, proportion of immune cell infiltration, and antitumor drug resistance. Furthermore, 86 differentially expressed genes (DEGs) between high- and low-risk groups were mainly enriched in immune-related pathways. The ILPM developed based on 26 prognostic immune-related lncRNAs can help in predicting the prognosis of patients suffering from gastric cancer. Precision medicine can be effectively carried out by dividing patients into high- and low-risk groups according to the RS.

摘要

长链非编码RNA(lncRNAs)在胃癌(GC)的免疫调节中发挥着重要作用。然而,免疫相关lncRNAs的临床应用价值尚未得到充分开发。基于当前研究克服胃癌患者预后预测和分类的挑战具有重要意义。在本研究中,使用R包ImmLnc获取癌症基因组图谱胃腺癌(TCGA-STAD)项目的免疫相关lncRNAs,并进行单变量Cox回归分析以寻找预后免疫相关lncRNAs。基于10种算法整合了总共117种组合,以确定免疫相关lncRNA预后模型(ILPM)。根据ILPM,采用最小绝对收缩和选择算子(LASSO)回归来寻找主要的lncRNAs并建立风险模型。使用单样本基因集富集分析(ssGSEA)、CIBERSORT算法、R包maftools、pRRophetic和clusterProfiler来测量风险组之间免疫细胞的比例、基因组突变差异、药物敏感性分析和通路富集分数。共发现321个免疫相关lncRNAs,其中有26个预后免疫相关lncRNAs。根据ILPM,从26个lncRNAs中选择了18个,由18个lncRNA特征构建的风险评分(RS)在TCGA训练集和基因表达综合数据库(GEO)验证数据集中具有良好的预测能力。根据中位RS将患者分为高风险组和低风险组,低风险组具有更好的预后、肿瘤免疫微环境和肿瘤特征富集分数,以及更高的代谢、基因组突变频率、免疫细胞浸润比例和抗肿瘤耐药性。此外,高风险组和低风险组之间的86个差异表达基因(DEGs)主要富集在免疫相关通路中。基于26个预后免疫相关lncRNAs开发的ILPM有助于预测胃癌患者的预后。根据RS将患者分为高风险组和低风险组可以有效地实施精准医学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca65/10111190/ab02423c0f7b/fgene-14-1106724-g001.jpg

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