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基于多组学数据分析建立透明细胞肾细胞癌患者的预后预测和药物选择模型。

Establishment of a Prognostic Prediction and Drug Selection Model for Patients with Clear Cell Renal Cell Carcinoma by Multiomics Data Analysis.

机构信息

Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.

Department of Urology, Changzheng Hospital, Naval Medical University, (Second Military Medical University), Shanghai, China.

出版信息

Oxid Med Cell Longev. 2022 Jan 4;2022:3617775. doi: 10.1155/2022/3617775. eCollection 2022.


DOI:10.1155/2022/3617775
PMID:35028006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8752262/
Abstract

METHODS: This study was based on the multiomics data (including mRNA, lncRNA, miRNA, methylation, and WES) of 258 ccRCC patients from TCGA database. Firstly, we screened the feature values that had impact on the prognosis and obtained two subtypes. Then, we used 10 algorithms to achieve multiomics clustering and conducted pseudotiming analysis to further validate the robustness of our clustering method, based on which the two subtypes of ccRCC patients were further subtyped. Meanwhile, the immune infiltration was compared between the two subtypes, and drug sensitivity and potential drugs were analyzed. Furthermore, to analyze the heterogeneity of patients at the multiomics level, biological functions between two subtypes were compared. Finally, Boruta and PCA methods were used for dimensionality reduction and cluster analysis to construct a renal cancer risk model based on mRNA expression. RESULTS: A prognosis predicting model of ccRCC was established by dividing patients into the high- and low-risk groups. It was found that overall survival (OS) and progression-free interval (PFI) were significantly different between the two groups ( < 0.01). The area under the OS time-dependent ROC curve for 1, 3, 5, and 10 years in the training set was 0.75, 0.72, 0.71, and 0.68, respectively. CONCLUSION: The model could precisely predict the prognosis of ccRCC patients and may have implications for drug selection for ccRCC patients.

摘要

方法:本研究基于 TCGA 数据库中 258 例 ccRCC 患者的多组学数据(包括 mRNA、lncRNA、miRNA、甲基化和 WES)。首先,我们筛选了对预后有影响的特征值,并获得了两个亚型。然后,我们使用 10 种算法进行多组学聚类,并进行伪时间分析,以进一步验证我们聚类方法的稳健性,在此基础上对 ccRCC 患者的两种亚型进行进一步亚分型。同时,比较两种亚型之间的免疫浸润情况,并分析药物敏感性和潜在药物。此外,为了在多组学水平上分析患者的异质性,比较了两种亚型之间的生物学功能。最后,使用 Boruta 和 PCA 方法进行降维和聚类分析,构建基于 mRNA 表达的肾癌风险模型。

结果:通过将患者分为高风险组和低风险组,建立了 ccRCC 的预后预测模型。发现两组患者的总生存期(OS)和无进展生存期(PFI)差异有统计学意义(<0.01)。在训练集中,OS 时间依赖性 ROC 曲线的 1、3、5 和 10 年 AUC 分别为 0.75、0.72、0.71 和 0.68。

结论:该模型能够准确预测 ccRCC 患者的预后,可能对 ccRCC 患者的药物选择有意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/2dadce3093cb/OMCL2022-3617775.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/6b2a08d69bc4/OMCL2022-3617775.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/15b78b0e113e/OMCL2022-3617775.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/58517f9646f1/OMCL2022-3617775.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/5f72f1dff7a0/OMCL2022-3617775.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/6551ce32c3df/OMCL2022-3617775.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/6a7aed25fc6f/OMCL2022-3617775.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/00827854c140/OMCL2022-3617775.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/f9543e828ec3/OMCL2022-3617775.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/2dadce3093cb/OMCL2022-3617775.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/6b2a08d69bc4/OMCL2022-3617775.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/15b78b0e113e/OMCL2022-3617775.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/58517f9646f1/OMCL2022-3617775.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/5f72f1dff7a0/OMCL2022-3617775.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/6551ce32c3df/OMCL2022-3617775.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/6a7aed25fc6f/OMCL2022-3617775.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/00827854c140/OMCL2022-3617775.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/f9543e828ec3/OMCL2022-3617775.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf9/8752262/2dadce3093cb/OMCL2022-3617775.009.jpg

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[8]
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本文引用的文献

[1]
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