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基于分子伴侣相关长链非编码RNA的肺腺癌预后模型及免疫治疗预测

Prognostic model and immunotherapy prediction based on molecular chaperone-related lncRNAs in lung adenocarcinoma.

作者信息

Xu Yue, Tao Tao, Li Shi, Tan Shuzhen, Liu Haiyan, Zhu Xiao

机构信息

Marine Medical Research Institute, Guangdong Medical University, Zhanjiang, China.

Department of Gastroscope, Zibo Central Hospital, Zibo, China.

出版信息

Front Genet. 2022 Oct 13;13:975905. doi: 10.3389/fgene.2022.975905. eCollection 2022.

Abstract

Molecular chaperones and long non-coding RNAs (lncRNAs) have been confirmed to be closely related to the occurrence and development of tumors, especially lung cancer. Our study aimed to construct a kind of molecular chaperone-related long non-coding RNAs (MCRLncs) marker to accurately predict the prognosis of lung adenocarcinoma (LUAD) patients and find new immunotherapy targets. In this study, we acquired molecular chaperone genes from two databases, Genecards and molecular signatures database (MsigDB). And then, we downloaded transcriptome data, clinical data, and mutation information of LUAD patients through the Cancer Genome Atlas (TCGA). MCRLncs were determined by Spearman correlation analysis. We used univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to construct risk models. Kaplan-meier (KM) analysis was used to understand the difference in survival between high and low-risk groups. Nomogram, calibration curve, concordance index (C-index) curve, and receiver operating characteristic (ROC) curve were used to evaluate the accuracy of the risk model prediction. In addition, we used gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses to explore the potential biological functions of MCRLncs. Immune microenvironmental landscapes were constructed by using single-sample gene set enrichment analysis (ssGSEA), tumor immune dysfunction and exclusion (TIDE) algorithm, "pRRophetic" R package, and "IMvigor210" dataset. The stem cell index based on mRNAsi expression was used to further evaluate the patient's prognosis. Sixteen MCRLncs were identified as independent prognostic indicators in patients with LUAD. Patients in the high-risk group had significantly worse overall survival (OS). ROC curve suggested that the prognostic features of MCRLncs had a good predictive ability for OS. Immune system activation was more pronounced in the high-risk group. Prognostic features of the high-risk group were strongly associated with exclusion and cancer-associated fibroblasts (CAF). According to this prognostic model, a total of 15 potential chemotherapeutic agents were screened for the treatment of LUAD. Immunotherapy analysis showed that the selected chemotherapeutic drugs had potential application value. Stem cell index mRNAsi correlates with prognosis in patients with LUAD. Our study established a kind of novel MCRLncs marker that can effectively predict OS in LUAD patients and provided a new model for the application of immunotherapy in clinical practice.

摘要

分子伴侣和长链非编码RNA(lncRNA)已被证实与肿瘤尤其是肺癌的发生发展密切相关。我们的研究旨在构建一种分子伴侣相关长链非编码RNA(MCRLnc)标志物,以准确预测肺腺癌(LUAD)患者的预后并寻找新的免疫治疗靶点。在本研究中,我们从Genecards和分子特征数据库(MsigDB)这两个数据库中获取分子伴侣基因。然后,我们通过癌症基因组图谱(TCGA)下载了LUAD患者的转录组数据、临床数据和突变信息。通过Spearman相关性分析确定MCRLnc。我们使用单因素、最小绝对收缩和选择算子(LASSO)以及多因素Cox回归分析来构建风险模型。采用Kaplan-Meier(KM)分析来了解高风险组和低风险组之间的生存差异。使用列线图、校准曲线、一致性指数(C指数)曲线和受试者工作特征(ROC)曲线来评估风险模型预测的准确性。此外,我们使用基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析来探索MCRLnc的潜在生物学功能。通过使用单样本基因集富集分析(ssGSEA)、肿瘤免疫功能障碍和排除(TIDE)算法、“pRRophetic”R包和“IMvigor210”数据集构建免疫微环境景观。基于mRNAsi表达的干细胞指数用于进一步评估患者的预后。16种MCRLnc被确定为LUAD患者的独立预后指标。高风险组患者的总生存期(OS)明显更差。ROC曲线表明,MCRLnc的预后特征对OS具有良好的预测能力。高风险组的免疫系统激活更为明显。高风险组的预后特征与排除和癌症相关成纤维细胞(CAF)密切相关。根据该预后模型,共筛选出15种潜在的化疗药物用于治疗LUAD。免疫治疗分析表明,所选化疗药物具有潜在应用价值。干细胞指数mRNAsi与LUAD患者的预后相关。我们的研究建立了一种新型的MCRLnc标志物,可有效预测LUAD患者的OS,并为免疫治疗在临床实践中的应用提供了新的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51de/9606628/98a49fb7be74/fgene-13-975905-g001.jpg

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