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坏死性凋亡相关长链非编码RNA预后模型与聚类分析:乳腺癌的预后预测及肿瘤浸润淋巴细胞

Necroptosis-Associated lncRNA Prognostic Model and Clustering Analysis: Prognosis Prediction and Tumor-Infiltrating Lymphocytes in Breast Cancer.

作者信息

Tao Shigui, Tao Kunlin, Cai Xiaoyong

机构信息

The General Surgery, The Second Affiliated Hospital of Guangxi Medical University, No. 166, Daxuedonglu Road, Nanning, Guangxi, China.

The People's Hospital, Guiping, Guangxi, China.

出版信息

J Oncol. 2022 Apr 27;2022:7099930. doi: 10.1155/2022/7099930. eCollection 2022.

Abstract

Necroptosis plays an important role in tumor genesis and progression. This study aims to identify necroptosis-related lncRNAs (NR-lncRNAs) in breast cancer (BC), and their prognostic value and relationship with the tumor immune environment (TIE) through bioinformatics. . A total of 67 necroptosis-related genes (NRGs) are retrieved, and 13 prognostically relevant NR-lncRNAs are identified by co-expression and Univariate Cox regression analyses. After unsupervised clustering analysis, the patients are classified into three clusters, and their survival and immune infiltration are compared. Lasso regression analysis is conducted to construct a prognostic model using eight lncRNAs (USP30-AS1, AC097662.1, AC007686.3, AL133467.1, AP006284.1, NDUFA6-DT, LINC01871, AL135818.1). The model is validated by Kaplan-Meier survival analysis, Multivariate Cox regression analysis, and receiver-operating characteristic (ROC) curves. Correlation analysis is useful to identify associations between risk scores and clinicopathological features. GSEA, drug prediction, and immune checkpoints analysis are further used to differentiate between the risk groups. . The C3 cluster has longer overall survival (OS) and the highest immune score, indicative of an immunologically hot tumor that may be sensitive to immunotherapy. Furthermore, the OS is significantly higher in the low-risk group, even after dividing the patients into subgroups with different clinical characteristics. The area under the ROC curve (AUC) for 1-, 3-, and 5-year survival in the training set are 0.761, 0.734, and 0.664, respectively, which indicate the moderate predictive performance of the model. . NR-lncRNAs can predict the prognosis of BC, distinguish between hot and cold tumors, and are potential predictive markers of the immunotherapy response.

摘要

坏死性凋亡在肿瘤的发生和发展中起重要作用。本研究旨在通过生物信息学方法鉴定乳腺癌(BC)中与坏死性凋亡相关的长链非编码RNA(NR-lncRNAs),及其预后价值以及与肿瘤免疫环境(TIE)的关系。共检索到67个与坏死性凋亡相关的基因(NRGs),并通过共表达和单变量Cox回归分析鉴定出13个与预后相关的NR-lncRNAs。经过无监督聚类分析,将患者分为三个簇,并比较它们的生存情况和免疫浸润情况。进行Lasso回归分析以使用8个lncRNAs(USP30-AS1、AC097662.1、AC007686.3、AL133467.1、AP006284.1、NDUFA6-DT、LINC01871、AL135818.1)构建预后模型。通过Kaplan-Meier生存分析、多变量Cox回归分析和受试者工作特征(ROC)曲线对该模型进行验证。相关性分析有助于确定风险评分与临床病理特征之间的关联。进一步使用基因集富集分析(GSEA)、药物预测和免疫检查点分析来区分风险组。C3簇具有更长的总生存期(OS)和最高的免疫评分,表明其为免疫热肿瘤,可能对免疫治疗敏感。此外,即使将患者分为具有不同临床特征的亚组,低风险组的OS也显著更高。训练集中1年、3年和5年生存的ROC曲线下面积(AUC)分别为0.761、0.734和0.664,这表明该模型具有中等预测性能。NR-lncRNAs可以预测BC的预后,区分热肿瘤和冷肿瘤,并且是免疫治疗反应的潜在预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f658/9068297/3768e6a0d42d/JO2022-7099930.008.jpg

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