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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00663

Urine metabolomics for renal cell carcinoma (RCC) prediction: tryptophan metabolism as an important pathway in RCC

xiaoyan liu1, mingxin zhang2, xiang liu1, haidan sun1, zhengguang guo1, xiaoyue tang1, zhan wang2, jing li1, hanzhong li2,  Wei Sun1* and yushi zhang2
  • 1Chinese Academy of Medical Sciences and Peking Union Medical College, China
  • 2Peking Union Medical College Hospital (CAMS), China

Abstract
Renal cell carcinoma (RCC) is the second most lethal urinary cancer. RCC is frequently asymptomatic and it is already metastatic at diagnosis. There is an urgent necessity for RCC specific biomarkers selection for diagnostic and prognostic purposes. In present study, we applied liquid chromatography - mass spectrometry (LC-MS) based metabolomics to analyze urine samples of 100 RCC, 34 benign kidney tumors and 129 healthy controls. Differential metabolites were analyzed to investigate if urine metabolites could differentiate RCC from non-RCC. A panel consisting of 9 metabolites showed the best predictive ability for RCC from the health controls with an area under the curve (AUC) values of 0.905 for the training dataset and 0.885 for the validation dataset. Separation was observed between the RCC and benign samples with an AUC of 0.816. RCC clinical stages (T1 and T2 vs. T3 and T4) could be separated using a panel of urine metabolites with an AUC of 0.813. One metabolite, N-formylkynurenine, was discovered to have potential value for RCC diagnosis from non-RCC subjects with an AUC of 0.808. Pathway enrichment analysis indicated that tryptophan metabolism was an important pathway in RCC. Our data concluded that urine metabolomics could be used for RCC diagnosis and would provide candidates for further targeted metabolomics analysis of RCC.

Keywords: Renal cell carcinoma, Metabolomics, Benign tumors, biomarker, tryptophan metabolism

Received: 12 Oct 2018; Accepted: 05 Jul 2019.

Edited by:

Marie-France Penet, School of Medicine, Johns Hopkins University, United States

Reviewed by:

Paloma V. Ballesteros, Facultad de Ciencias, Universidad Nacional de Educación a Distancia, Spain
Tone F. Bathen, Norwegian University of Science and Technology, Norway  

Copyright: © 2019 liu, zhang, liu, sun, guo, tang, wang, li, li, Sun and zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Wei Sun, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, Beijing Municipality, China, sunwei1018@sina.com