Development and Validation of a Novel Hypoxia-Related Long Noncoding RNA Model With Regard to Prognosis and Immune Features in Breast Cancer.
Development and Validation of a Novel Hypoxia-Related Long Noncoding RNA Model With Regard to Prognosis and Immune Features in Breast Cancer.
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DOI：
10.3389/fcell.2021.796729
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发表时间：
2021
影响因子：
5.5
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Gu P;Zhang L;Wang R;Ding W;Wang W;Liu Y;Wang W;Li Z;Yan B;Sun X
背景：女性乳腺癌是目前世界上最常见的癌症。本研究旨在开发和验证一种新的缺氧相关长非编码RNA（HRL）预后模型，用于预测乳腺癌患者的总生存期（OS）。 方法：从TCGA数据库下载基因表达谱。从分子签名数据库中获得了总共200个缺氧相关的mRNA。采用斯皮尔曼等级相关法对缺氧相关mRNA和lncRNA进行共表达分析，筛选出166个HRL。基于训练集的单变量考克斯回归和最小绝对收缩和选择算子考克斯回归分析，我们筛选出12个最佳预后缺氧相关lncRNA（PHRL），以建立预后模型。Kaplan-Meier生存分析、受试者工作特征曲线、曲线下面积、单变量和多变量考克斯回归分析用于检验风险模型在训练集、测试集和总集中的预测能力。 结果：建立了一个12-HRL预后模型，用于预测乳腺癌患者的生存结局。与低风险组相比，高风险组患者的中位OS、DFS（无病生存期）显著缩短，预测化疗敏感性（紫杉醇、多西他赛）较低。此外，基于12个HRL表达的风险评分作为独立的预后因素。免疫细胞浸润分析显示，高危组患者的免疫评分低于低危组患者。进行RT-qPCR测定以验证12种PHRL在乳腺癌组织和细胞系中的表达。 结论：我们的研究发现了数十种与乳腺癌缺氧信号通路相关的潜在预后生物标志物和治疗靶点。
Background: Female breast cancer is currently the most frequently diagnosed cancer in the world. This study aimed to develop and validate a novel hypoxia-related long noncoding RNA (HRL) prognostic model for predicting the overall survival (OS) of patients with breast cancer. Methods: The gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 200 hypoxia-related mRNAs were obtained from the Molecular Signatures Database. The co-expression analysis between differentially expressed hypoxia-related mRNAs and lncRNAs based on Spearman’s rank correlation was performed to screen out 166 HRLs. Based on univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis in the training set, we filtered out 12 optimal prognostic hypoxia-related lncRNAs (PHRLs) to develop a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic curves, area under the curve, and univariate and multivariate Cox regression analyses were used to test the predictive ability of the risk model in the training, testing, and total sets. Results: A 12-HRL prognostic model was developed to predict the survival outcome of patients with breast cancer. Patients in the high-risk group had significantly shorter median OS, DFS (disease-free survival), and predicted lower chemosensitivity (paclitaxel, docetaxel) compared with those in the low-risk group. Also, the risk score based on the expression of the 12 HRLs acted as an independent prognostic factor. The immune cell infiltration analysis revealed that the immune scores of patients in the high-risk group were lower than those of the patients in the low-risk group. RT-qPCR assays were conducted to verify the expression of the 12 PHRLs in breast cancer tissues and cell lines. Conclusion: Our study uncovered dozens of potential prognostic biomarkers and therapeutic targets related to the hypoxia signaling pathway in breast cancer.
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