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Validation of CT radiomics for prediction of distant metastasis after surgical resection in patients with clear cell renal cell carcinoma: exploring the underlying signaling pathways

  • Imaging Informatics and Artificial Intelligence
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To develop a radiomics model using preoperative multiphasic CT for predicting distant metastasis after surgical resection in patients with localized clear cell renal cell carcinoma (ccRCC) and to identify key biological pathways underlying the predictive radiomics features using RNA sequencing data.

Methods

In this multi-institutional retrospective study, a CT radiomics metastasis score (RMS) was developed from a radiomics analysis cohort (n = 184) for distant metastasis prediction. Using a gene expression analysis cohort (n = 326), radiomics-associated gene modules were identified. Based on a radiogenomics discovery cohort (n = 42), key biological pathways were enriched from the gene modules. Furthermore, a multigene signature associated with RMS was constructed and validated on an independent radiogenomics validation cohort (n = 37).

Results

The 9-feature-based RMS predicted distant metastasis with an AUC of 0.861 in validation set and was independent with clinical factors (p < 0.001). A gene module comprising 114 genes was identified to be associated with all nine radiomics features (p < 0.05). Four enriched pathways were identified, including ECM-receptor interaction, focal adhesion, protein digestion and absorption, and PI3K-Akt pathways. Most of them play important roles in tumor progression and metastasis. A 19-gene signature was constructed from the radiomics-associated gene module and predicted metastasis with an AUC of 0.843 in the radiogenomics validation cohort.

Conclusions

CT radiomics features can predict distant metastasis after surgical resection of localized ccRCC while the predictive radiomics phenotypes may be driven by key biological pathways related to cancer progression and metastasis.

Key Points

• Radiomics features from primary tumor in preoperative CT predicted distant metastasis after surgical resection in patients with localized ccRCC.

• CT radiomics features predictive of distant metastasis were associated with key signaling pathways related to tumor progression and metastasis.

• Gene signature associated with radiomics metastasis score predicted distant metastasis in localized ccRCC.

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Abbreviations

ccRCC:

Clear cell renal cell carcinoma

CM:

Corticomedullary phase

ECM:

Extracellular matrix

FDR:

False discovery rate

GLCM:

Gray level co-occurrence matrix

GLDM:

Gray level dependency matrix

GLRLM:

Gray level run length matrix

GLSZM:

Gray level size matrix

KEGG:

KOBAS-Kyoto Encyclopedia of Genes and Genomes

LASSO:

Least absolute shrinkage and selection operator

NG:

Nephrographic phase

NGTDM:

Neighborhood gray tone difference matrix

PI3K:

Phosphoinositide 3-kinases

RMS:

Radiomics metastasis score

Se:

Sensitivity

Sp:

Specificity

TCGA:

The cancer genome atlas

TCIA:

The cancer imaging archive

UE:

Unenhanced scans

WGCNA:

Weighted gene co-expression network analysis

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Funding

This study has received funding by National Natural Science Foundation of China (61901458), China Postdoctoral Science Foundation (2019 M663187), Youth Innovation Promotion Association of Chinese Academy of Sciences (2018364), and Shenzhen Basic Research Program (JCYJ20170413162354654).

Author information

Author notes

  1. Yuanshen Zhao and Guiqin Liu contributed equally to this work.

Authors and Affiliations

  1. Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, No. 1068, Xueyuan Avenue, Shenzhen, 518055, Guangdong Province, China

    Yuanshen Zhao, Qiuchang Sun & Zhi-Cheng Li

  2. Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630, Dongfang Road, Pudong, Shanghai, 200127, China

    Guiqin Liu & Guangyu Wu

  3. School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Guangtao Zhai

Authors
  1. Yuanshen Zhao
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  2. Guiqin Liu
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  3. Qiuchang Sun
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  4. Guangtao Zhai
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  5. Guangyu Wu
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  6. Zhi-Cheng Li
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Corresponding authors

Correspondence to Guangyu Wu or Zhi-Cheng Li.

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The guarantor of this publication is Zhi-Cheng Li.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors (Zhi-Cheng Li) has significant statistical expertise.

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Written informed consent was waved by the Institutional Review Board.

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Institutional Review Board approval was obtained.

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• retrospective

• diagnostic or prognostic study

• performed at multiple institution

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Zhao, Y., Liu, G., Sun, Q. et al. Validation of CT radiomics for prediction of distant metastasis after surgical resection in patients with clear cell renal cell carcinoma: exploring the underlying signaling pathways. Eur Radiol 31, 5032–5040 (2021). https://doi.org/10.1007/s00330-020-07590-2

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  • DOI: https://doi.org/10.1007/s00330-020-07590-2

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