Identification and validation of stemness-related lncRNA prognostic signature for breast cancer
Identification and validation of stemness-related lncRNA prognostic signature for breast cancer
复制标题
乳腺癌干性相关 lncRNA 预后特征的鉴定和验证
DOI：
10.1186/s12967-020-02497-4
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发表时间：
2020-08-31
影响因子：
7.4
通讯作者：
Jin, Feng
中科院分区：
文献类型：
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作者：
Li, Xiaoying;Li, Yang;Jin, Feng
背景长非编码RNA(Long Non Coding RNAs，LncRNAs)是乳腺癌发生发展的重要因素，参与乳腺癌干细胞(BCSCs)的干性调节。IncRNAs与乳腺癌患者的预后密切相关。从肿瘤基因组图谱(TCGA)中构建BCSC相关mRNAs-lncRNAs共表达网络(TCGA)。使用单变量和多变量Cox比例风险分析来确定具有预后价值的干性风险模型。采用Kaplan-Meier分析、单因素和多因素COX回归分析及受试者工作特征(ROC)曲线分析对风险模型进行验证。采用主成分分析(PCA)和基因集丰富分析(GSEA)功能注释方法对风险模型进行分析。我们评估了这些与BCSC相关的LncRNA的预后价值，最终得到了由12个与BCSC相关的LncRNA(Z68871.1、LINC00578、AC097639.1、AP003119.3、AP001207.3、LINC00668、AL122010.1、AC245297.3、LINC01871、AP000851.2、AC022509.2和SEMA3B-AS1)组成的预后风险模型。基于计算的风险分数，风险模型被进一步验证为乳腺癌患者的一个新的独立预后因素。此外，基于风险模型，低风险组和高风险组表现出不同的干性状态。结论12个BCSC相关的lncRNA特征可能是乳腺癌的一个有前景的预后因素，并可在临床实践中促进BCSC相关治疗的管理。
BackgroundLong noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer.MethodsA co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan–Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model.ResultsIn this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncRNAs (Z68871.1, LINC00578, AC097639.1, AP003119.3, AP001207.3, LINC00668, AL122010.1, AC245297.3, LINC01871, AP000851.2, AC022509.2 and SEMA3B-AS1). The risk model was further verified as a novel independent prognostic factor for breast cancer patients based on the calculated risk score. Moreover, based on the risk model, the low- risk and high-risk groups displayed different stemness statuses.ConclusionsThese findings suggested that the 12 BCSC-related lncRNA signature might be a promising prognostic factor for breast cancer and can promote the management of BCSC-related therapy in clinical practice.