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基于贝叶斯 Spike-and-Slab Lasso 方法鉴定透明细胞肾细胞癌中的外泌体相关长非编码 RNA。

Identification of exosomes-related lncRNAs in clear cell renal cell carcinoma based on Bayesian spike-and-slab lasso approach.

机构信息

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.

出版信息

Funct Integr Genomics. 2023 Feb 20;23(1):62. doi: 10.1007/s10142-023-00985-6.

Abstract

Exosomes-related long non-coding RNAs (lncRNAs) have been reported to play significant roles in clear cell renal cell carcinoma (ccRCC). However, there is little known about the relationship between exosomes-related lncRNAs and ccRCC. This study aimed to select optimal prognostic model based on exosomes-related lncRNAs to provide a methodological reference for high-dimensional data. Based on the Cancer Genome Atlas (TCGA) database of 515 ccRCC patients, two risk score models were generated underlying Bayesian spike-and-slab lasso and lasso regression. The optimal model was determined by calculating the area of time-dependent receiver-operating characteristic (ROC) curves in the TCGA and ArrayExpress databases. The immune patterns and sensitivity of immunotherapy between the high and low groups were further explored. Initially, we constructed two risk score models containing 11 and 7 exosomes-related lncRNAs according to Bayesian spike-and-slab lasso and lasso regression respectively. ROC curves revealed that the model constructed by Bayesian spike-and-slab lasso regression was more reliable in predicting survival at 1, 3, and 5 years, yielding an area under the curves (AUCs) of 0.796, 0.732, and 0.742, respectively. Kaplan-Meier (K-M) curves presented that prognosis was poorer in the high-risk score group (P < 0.001). Additionally, the high-risk score group patients were enriched in immune-activating phenotypes and more sensitive to immunotherapy. The exosomes-related lncRNAs model constructed with Bayesian spike-and-slab lasso regression has higher predictive power for ccRCC patients' prognosis, which provides methodological reference for the analysis of high-dimensional data in bioinformatics and guides the tailored treatment of ccRCC patients.

摘要

外泌体相关长链非编码 RNA(lncRNA)已被报道在透明细胞肾细胞癌(ccRCC)中发挥重要作用。然而,关于外泌体相关 lncRNA 与 ccRCC 的关系知之甚少。本研究旨在基于外泌体相关 lncRNA 选择最佳预后模型,为高维数据提供方法学参考。基于 515 例 ccRCC 患者的癌症基因组图谱(TCGA)数据库,采用贝叶斯 Spike-and-slab lasso 和 lasso 回归生成两个风险评分模型。通过计算 TCGA 和 ArrayExpress 数据库中时间依赖性接收者操作特征(ROC)曲线的面积来确定最佳模型。进一步探讨高、低组间免疫模式和免疫治疗敏感性。最初,我们根据贝叶斯 Spike-and-slab lasso 和 lasso 回归分别构建了两个包含 11 个和 7 个外泌体相关 lncRNA 的风险评分模型。ROC 曲线显示,贝叶斯 Spike-and-slab lasso 回归构建的模型在预测 1、3 和 5 年生存率方面更为可靠,曲线下面积(AUCs)分别为 0.796、0.732 和 0.742。Kaplan-Meier(K-M)曲线显示,高风险评分组的预后更差(P<0.001)。此外,高风险评分组患者的免疫激活表型更为丰富,对免疫治疗更为敏感。基于贝叶斯 Spike-and-slab lasso 回归构建的外泌体相关 lncRNA 模型对 ccRCC 患者预后的预测能力更高,为生物信息学中高维数据的分析提供了方法学参考,并指导 ccRCC 患者的个体化治疗。

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