Urine-Based Metabolomics and Machine Learning Reveals Metabolites Associated with Renal Cell Carcinoma Stage

Cancers

Arthur S. Edison¹  Olatomiwa O. Bifarin¹  Sharon H. Bergquist²  David L. Roberts²  Rebecca S. Arnold³  Kenneth Ogan³  John A. Petros³  Viraj A. Master³  David A. Gaul⁴  Facundo M. Fernández⁴  Samyukta Sah⁴ 

[1] Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA;Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA;Department of Urology, Emory University, Atlanta, GA 30308, USA;School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA;

关键词: renal cell carcinoma;    metabolomics;    machine learning;    liquid chromatography-mass spectrometry;    nuclear magnetic resonance spectroscopy;    biomarker;   

DOI  :  10.3390/cancers13246253

来源: DOAJ

【 摘 要 】

Urine metabolomics profiling has potential for non-invasive RCC staging, in addition to providing metabolic insights into disease progression. In this study, we utilized liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and machine learning (ML) for the discovery of urine metabolites associated with RCC progression. Two machine learning questions were posed in the study: Binary classification into early RCC (stage I and II) and advanced RCC stages (stage III and IV), and RCC tumor size estimation through regression analysis. A total of 82 RCC patients with known tumor size and metabolomic measurements were used for the regression task, and 70 RCC patients with complete tumor-nodes-metastasis (TNM) staging information were used for the classification tasks under ten-fold cross-validation conditions. A voting ensemble regression model consisting of elastic net, ridge, and support vector regressor predicted RCC tumor size with a R² value of 0.58. A voting classifier model consisting of random forest, support vector machines, logistic regression, and adaptive boosting yielded an AUC of 0.96 and an accuracy of 87%. Some identified metabolites associated with renal cell carcinoma progression included 4-guanidinobutanoic acid, 7-aminomethyl-7-carbaguanine, 3-hydroxyanthranilic acid, lysyl-glycine, glycine, citrate, and pyruvate. Overall, we identified a urine metabolic phenotype associated with renal cell carcinoma stage, exploring the promise of a urine-based metabolomic assay for staging this disease.

【 授权许可】

Unknown