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一个与乳腺癌免疫浸润和肿瘤突变负荷相关的 lncRNA 预后标志物。

A lncRNA prognostic signature associated with immune infiltration and tumour mutation burden in breast cancer.

机构信息

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Cell Mol Med. 2020 Nov;24(21):12444-12456. doi: 10.1111/jcmm.15762. Epub 2020 Sep 23.

Abstract

Current studies have shown that long non-coding RNAs (lncRNAs) may serve as prognostic biomarkers in multiple cancers. Therefore, we postulated that expression patterns of multiple lncRNAs combined into a single signature could improve clinicopathological risk stratification and prediction of overall survival rate for breast cancer patients. Two algorithms, Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were used to select candidate lncRNAs. Univariate and multivariate Cox regression analyses were employed to construct a seven-lncRNA signature for breast cancer. Stratified analysis revealed that the signature was significantly associated with multiple clinicopathological risk factors. For clinical use, we developed a nomogram model to predict overall survival and odds of death for breast cancer patients. Single-sample gene set enrichment analysis (ssGSEA), CIBERSORT algorithm and ESTIMATE method were employed to assess the relative immune cell infiltrations of each sample. Differentially infiltration of immune cells and diverse tumour mutation burden (TMB) scores might give rise to the efficacy of lncRNA signature for predicting the overall survival of patients. Correlation analysis implied that LINC01215 was associated with multiple immune-related signalling pathways. A seven-lncRNA prognostic signature is a reliable tool to predict the prognosis of breast cancer patients.

摘要

目前的研究表明,长链非编码 RNA(lncRNAs)可能作为多种癌症的预后生物标志物。因此,我们假设将多个 lncRNA 的表达模式组合成一个单一的特征可以改善乳腺癌患者的临床病理风险分层和总生存率预测。使用最小绝对值收缩和选择操作(LASSO)和支持向量机-递归特征消除(SVM-RFE)两种算法来选择候选 lncRNA。单因素和多因素 Cox 回归分析用于构建乳腺癌的七个 lncRNA 特征。分层分析表明,该特征与多个临床病理危险因素显著相关。为了临床应用,我们开发了一个列线图模型来预测乳腺癌患者的总生存率和死亡概率。采用单样本基因集富集分析(ssGSEA)、CIBERSORT 算法和 ESTIMATE 方法评估每个样本的相对免疫细胞浸润情况。免疫细胞的差异浸润和不同的肿瘤突变负担(TMB)评分可能导致 lncRNA 特征预测患者总生存率的效果。相关性分析表明,LINC01215 与多种免疫相关信号通路有关。七个 lncRNA 预后特征是预测乳腺癌患者预后的可靠工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84cd/7687003/3b78f5075959/JCMM-24-12444-g001.jpg

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