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缺氧相关 lncRNA 特征的综合分析预测肺腺癌患者的预后和免疫微环境。

Integrated analysis of hypoxia-associated lncRNA signature to predict prognosis and immune microenvironment of lung adenocarcinoma patients.

机构信息

Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Geriatric Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Bioengineered. 2021 Dec;12(1):6186-6200. doi: 10.1080/21655979.2021.1973874.

Abstract

Lung adenocarcinoma (LUAD) represents the main lung cancer (LC) subtype that possesses a disappointing clinical outcome over the decades. Tumor hypoxia is closely bound up with dismal survival for malignant tumor cases. We identified hypoxia-associated long non-coding RNA (lncRNA) signature to be an explicit indicator for predicting prognosis. The present work acquired RNA-seq and associated clinical data from The Cancer Genome Atlas (TCGA) database. Consensus cluster analysis characterized the hypoxia status of LUAD patients. Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) method determined significantly prognosis-related lncRNAs which were used to create a prognostic model. Diverse statistical approaches like the Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and nomogram were adopted to verify the accuracy of the risk score. The potential immune environment landscape was unearthed by the CIBERSORT algorithm. Three hypoxia-related clusters were determined and 221 differentially expressed hypoxia-related lncRNAs were screened out. We developed a new predictive model based on seven lncRNAs (LINC00941, AC022784.1, AC079949.2, LINC00707, AL161431.1, AC010980.2 and AC090001.1). Kaplan-Meier curves and ROC plots uncovered the reliable predictive power of the risk score model. In addition, the immunosuppressive landscape was presented in the high-risk group by immune cell infiltration analysis. The seven hypoxia lncRNAs survival signature in our article are robust, accurate tools for predicting overall survival in LUAD patients.

摘要

肺腺癌(LUAD)是主要的肺癌(LC)亚型,几十年来其临床预后一直较差。肿瘤缺氧与恶性肿瘤患者的不良预后密切相关。我们发现与缺氧相关的长链非编码 RNA(lncRNA)特征是预测预后的明确指标。本研究从癌症基因组图谱(TCGA)数据库中获取了 RNA-seq 和相关临床数据。共识聚类分析对 LUAD 患者的缺氧状态进行了特征描述。Cox 回归分析和最小绝对收缩和选择算子(LASSO)方法确定了与预后显著相关的 lncRNA,用于构建预后模型。采用 Kaplan-Meier 曲线、受试者工作特征(ROC)曲线和列线图等多种统计方法验证风险评分的准确性。通过 CIBERSORT 算法揭示潜在的免疫环境景观。确定了三个与缺氧相关的聚类,并筛选出 221 个差异表达的与缺氧相关的 lncRNA。我们基于七个 lncRNA(LINC00941、AC022784.1、AC079949.2、LINC00707、AL161431.1、AC010980.2 和 AC090001.1)建立了一个新的预测模型。Kaplan-Meier 曲线和 ROC 图揭示了风险评分模型可靠的预测能力。此外,通过免疫细胞浸润分析,在高危组中呈现了免疫抑制景观。我们文章中的七个与缺氧相关的 lncRNA 生存特征是 LUAD 患者总体生存的稳健、准确的预测工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c7/8806605/6f15a36fc9c5/KBIE_A_1973874_F0001_OC.jpg

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