Research Paper Volume 13, Issue 7 pp 9960—9975

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

Hao Zeng1, *, , Linyan Chen1, *, , Manni Wang1, *, , Yuling Luo2, , Yeqian Huang2, , Xuelei Ma1, ,

  • 1 Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center, Chengdu, China
  • 2 West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
* Co-first authors

Received: December 11, 2020       Accepted: February 18, 2021       Published: March 26, 2021
How to Cite

Copyright: © 2021 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 VHL (AUC=0.971), BAP1 (AUC=0.955), PBRM1 (AUC=0.972), SETD2 (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.


ccRCC: clear cell renal cell carcinoma; GLCM: gray-level co-occurrence matrix; GLDM: gray-level dependence matrix; GLRLM: gray-level run length matrix; GLSZM: gray-level size zone matrix; NGTDM: neighborhood gray tone difference matrix; GBDT: gradient boosting decision tree; LASSO: least absolute shrinkage and selection operator; RF: random forest; XGBoost: extreme gradient boosting; AdaBoost: adaptive boosting; LR: logistic regression; DT: decision tree; SVM: support vector machine; NB: naive Bayesian; KNN: K-nearest neighbor; DEGs: differently expressed genes.