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整合放射基因组学分析预测透明细胞肾细胞癌的分子特征和生存。

Integrative radiogenomics analysis for predicting molecular features and survival in clear cell renal cell carcinoma.

机构信息

Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center, Chengdu, China.

West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Aging (Albany NY). 2021 Mar 26;13(7):9960-9975. doi: 10.18632/aging.202752.


DOI:10.18632/aging.202752
PMID:33795526
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8064160/
Abstract

OBJECTIVES: To assess the feasibility of predicting molecular characteristics by computed tomography (CT) radiomics features, and predicting overall survival (OS) using combination of omics data in clear cell renal cell carcinoma (ccRCC). METHODS: Genetic data of 207 ccRCC patients was retrieved from The Cancer Genome Atlas (TCGA) and matched contrast-enhanced CT images were obtained from The Cancer Imaging Archive (TCIA). Another cohort of 175 ccRCC patients from West China Hospital was used as external validation. We first applied radiomics features and machine learning algorithms to predict genetic mutations and mRNA-based molecular subtypes. Next, we established predictive models for OS based on single omics, combined omics (radiomics+genomics, radiomics+transcriptomics, radiomics+proteomics) and all features (multi-omics). RESULTS: Using radiomics features, random forest algorithm showed good capacity to identify the mutations (AUC=0.971), (AUC=0.955), (AUC=0.972), (AUC=0.949), and molecular subtypes m1 (AUC=0.973), m2 (AUC=0.968), m3 (AUC=0.961), m4 (AUC=0.953). The TCGA cohort was divided into training (n=104) and validation (n=103) sets. The radiomics model had promising prognostic value for OS in validation set (5-year AUC=0.775) and external validation set (5-year AUC=0.755). In the validation set, the radiomics+omics models enhanced predictive accuracy than single-omics models, and the multi-omics model made further improvement (5-year AUC=0.846). High-risk group of validation set predicted by multi-omics model showed significantly poorer OS (HR=6.20, 95%CI: 3.19-8.44, p<0.0001). CONCLUSIONS: CT radiomics might be a feasible approach to predict genetic mutations, molecular subtypes and OS in ccRCC patients. Integrative analysis of radiogenomics may improve the survival prediction of ccRCC patients.

摘要

目的:评估通过计算机断层扫描(CT)放射组学特征预测分子特征的可行性,并结合透明细胞肾细胞癌(ccRCC)中的组学数据预测总生存期(OS)。

方法:从癌症基因组图谱(TCGA)中检索 207 例 ccRCC 患者的遗传数据,并从癌症成像档案(TCIA)中获得匹配的增强 CT 图像。华西医院的另一个 175 例 ccRCC 患者队列被用作外部验证。我们首先应用放射组学特征和机器学习算法来预测基因突变和基于 mRNA 的分子亚型。接下来,我们基于单组学、联合组学(放射组学+基因组学、放射组学+转录组学、放射组学+蛋白质组学)和所有特征(多组学)建立 OS 预测模型。

结果:使用放射组学特征,随机森林算法显示出识别突变的良好能力(AUC=0.971)、(AUC=0.955)、(AUC=0.972)、(AUC=0.949)和分子亚型 m1(AUC=0.973)、m2(AUC=0.968)、m3(AUC=0.961)、m4(AUC=0.953)。TCGA 队列分为训练(n=104)和验证(n=103)组。放射组学模型在验证组(5 年 AUC=0.775)和外部验证组(5 年 AUC=0.755)中具有良好的预后价值。在验证组中,放射组学+组学模型比单组学模型具有更高的预测准确性,而多组学模型则进一步提高(5 年 AUC=0.846)。多组学模型预测的验证组高危组 OS 明显较差(HR=6.20,95%CI:3.19-8.44,p<0.0001)。

结论:CT 放射组学可能是预测 ccRCC 患者基因突变、分子亚型和 OS 的一种可行方法。放射基因组学的综合分析可能会提高 ccRCC 患者的生存预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/d713107d1774/aging-13-202752-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/95de2dc3c0b2/aging-13-202752-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/bb103e2d8a17/aging-13-202752-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/5b75a0105b43/aging-13-202752-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/d233339ec57e/aging-13-202752-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/e6746039c232/aging-13-202752-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/d713107d1774/aging-13-202752-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/95de2dc3c0b2/aging-13-202752-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/bb103e2d8a17/aging-13-202752-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/5b75a0105b43/aging-13-202752-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/d233339ec57e/aging-13-202752-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/e6746039c232/aging-13-202752-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29f/8064160/d713107d1774/aging-13-202752-g006.jpg

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本文引用的文献

[1]
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[2]
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Machine learning-based unenhanced CT texture analysis for predicting BAP1 mutation status of clear cell renal cell carcinomas.

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