乳腺癌中与免疫浸润和肿瘤突变负荷相关的lncRNA预后特征

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Journal of Cellular and Molecular Medicine Pub Date : 2020-11-01 Epub Date: 2020-09-23 DOI:10.1111/jcmm.15762
Zijian Liu, Mi Mi, Xiaoqian Li, Xin Zheng, Gang Wu, Liling Zhang
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引用次数: 64

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,我们假设多个lncrna组合成一个单一特征的表达模式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。采用最小绝对收缩和选择运算(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。采用单因素和多因素Cox回归分析构建乳腺癌的7个lncrna特征。分层分析显示,该特征与多种临床病理危险因素显著相关。对于临床应用,我们开发了一个nomogram模型来预测乳腺癌患者的总生存率和死亡几率。采用单样本基因集富集分析(ssGSEA)、CIBERSORT算法和ESTIMATE方法评估各样本的相对免疫细胞浸润情况。不同的免疫细胞浸润和不同的肿瘤突变负担(TMB)评分可能导致lncRNA标记在预测患者总生存期方面的有效性。相关分析提示LINC01215与多种免疫相关信号通路相关。7 - lncrna预后标记是预测乳腺癌患者预后的可靠工具。
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A lncRNA prognostic signature associated with immune infiltration and tumour mutation burden in breast cancer.

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.

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来源期刊
CiteScore
10.00
自引率
1.90%
发文量
496
审稿时长
28 weeks
期刊介绍: Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.
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