Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma

Yeqian Huang; Hao Zeng; Linyan Chen; Yuling Luo; Xuelei Ma; Ye Zhao

doi:10.3389/fonc.2021.640881

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma

Front Oncol. 2021 Mar 8:11:640881. doi: 10.3389/fonc.2021.640881. eCollection 2021.

Authors

Yeqian Huang^{1

2}, Hao Zeng^{1

3}, Linyan Chen^{1

3}, Yuling Luo^{1

3}, Xuelei Ma^{1

3}, Ye Zhao⁴

Affiliations

¹ Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
² West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.
³ State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
⁴ School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies in urinary system, and radiomics has been adopted in tumor staging and prognostic evaluation in renal carcinomas. This study aimed to integrate image features of contrast-enhanced CT and underlying genomics features to predict the overall survival (OS) of ccRCC patients.

Method: We extracted 107 radiomics features out of 205 patients with available CT images obtained from TCIA database and corresponding clinical and genetic information from TCGA database. LASSO-COX and SVM-RFE were employed independently as machine-learning algorithms to select prognosis-related imaging features (PRIF). Afterwards, we identified prognosis-related gene signature through WGCNA. The random forest (RF) algorithm was then applied to integrate PRIF and the genes into a combined imaging-genomics prognostic factors (IGPF) model. Furthermore, we constructed a nomogram incorporating IGPF and clinical predictors as the integrative prognostic model for ccRCC patients.

Results: A total of four PRIF and four genes were identified as IGPF and were represented by corresponding risk score in RF model. The integrative IGPF model presented a better prediction performance than the PRIF model alone (average AUCs for 1-, 3-, and 5-year were 0.814 vs. 0.837, 0.74 vs. 0.806, and 0.689 vs. 0.751 in test set). Clinical characteristics including gender, TNM stage and IGPF were independent risk factors. The nomogram integrating clinical predictors and IGPF provided the best net benefit among the three models.

Conclusion: In this study we established an integrative prognosis-related nomogram model incorporating imaging-genomic features and clinical indicators. The results indicated that IGPF may contribute to a comprehensive prognosis assessment for ccRCC patients.

Keywords: clear cell renal cell carcinoma; genomics; machine learning; prognosis; radiomics.