Identification of novel neuroblastoma biomarkers in urine samples
Abstract Urine is a complex liquid containing numerous small molecular metabolites. The ability to non-invasively test for cancer biomarkers in urine is especially beneficial for screening child patients. This study attempted to identify neuroblastoma biomarkers by comprehensively analysing urinary...
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2021-02-01
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Online Access: | https://doi.org/10.1038/s41598-021-83619-w |
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doaj-c32edc81ed5a4d7c98de512961cdbfdc2021-02-21T12:33:51ZengNature Publishing GroupScientific Reports2045-23222021-02-011111910.1038/s41598-021-83619-wIdentification of novel neuroblastoma biomarkers in urine samplesKazuki Yokota0Hiroo Uchida1Minoru Sakairi2Mayumi Abe3Yujiro Tanaka4Takahisa Tainaka5Chiyoe Shirota6Wataru Sumida7Kazuo Oshima8Satoshi Makita9Hizuru Amano10Akinari Hinoki11Department of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineHitachi, Ltd., R & D Group, Centre for Exploratory ResearchHitachi, Ltd., R & D Group, Centre for Exploratory ResearchDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineDepartment of Paediatric Surgery, Nagoya University Graduate School of MedicineAbstract Urine is a complex liquid containing numerous small molecular metabolites. The ability to non-invasively test for cancer biomarkers in urine is especially beneficial for screening child patients. This study attempted to identify neuroblastoma biomarkers by comprehensively analysing urinary metabolite samples from children. A total of 87 urine samples were collected from 54 participants (15 children with neuroblastoma and 39 without cancer) and used to perform a comprehensive analysis. Urine metabolites were extracted using liquid chromatography/mass spectrometry and analysed by Metabolon, Inc. Biomarker candidates were extracted using the Wilcoxon rank sum test, random forest method (RF), and orthogonal partial least squares discriminant analysis (OPLS-DA). RF identified three important metabolic pathways in 15 samples from children with neuroblastoma. One metabolite was selected from each of the three identified pathways and combined to create a biomarker candidate (3-MTS, CTN, and COR) that represented each of the three pathways; using this candidate, all 15 cases were accurately distinguishable from the control group. Two cases in which known biomarkers were negative tested positive using this new biomarker. Furthermore, the predictive value did not decrease in cases with a low therapeutic effect. This approach could be effectively applied to identify biomarkers for other cancer types.https://doi.org/10.1038/s41598-021-83619-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kazuki Yokota Hiroo Uchida Minoru Sakairi Mayumi Abe Yujiro Tanaka Takahisa Tainaka Chiyoe Shirota Wataru Sumida Kazuo Oshima Satoshi Makita Hizuru Amano Akinari Hinoki |
spellingShingle |
Kazuki Yokota Hiroo Uchida Minoru Sakairi Mayumi Abe Yujiro Tanaka Takahisa Tainaka Chiyoe Shirota Wataru Sumida Kazuo Oshima Satoshi Makita Hizuru Amano Akinari Hinoki Identification of novel neuroblastoma biomarkers in urine samples Scientific Reports |
author_facet |
Kazuki Yokota Hiroo Uchida Minoru Sakairi Mayumi Abe Yujiro Tanaka Takahisa Tainaka Chiyoe Shirota Wataru Sumida Kazuo Oshima Satoshi Makita Hizuru Amano Akinari Hinoki |
author_sort |
Kazuki Yokota |
title |
Identification of novel neuroblastoma biomarkers in urine samples |
title_short |
Identification of novel neuroblastoma biomarkers in urine samples |
title_full |
Identification of novel neuroblastoma biomarkers in urine samples |
title_fullStr |
Identification of novel neuroblastoma biomarkers in urine samples |
title_full_unstemmed |
Identification of novel neuroblastoma biomarkers in urine samples |
title_sort |
identification of novel neuroblastoma biomarkers in urine samples |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-02-01 |
description |
Abstract Urine is a complex liquid containing numerous small molecular metabolites. The ability to non-invasively test for cancer biomarkers in urine is especially beneficial for screening child patients. This study attempted to identify neuroblastoma biomarkers by comprehensively analysing urinary metabolite samples from children. A total of 87 urine samples were collected from 54 participants (15 children with neuroblastoma and 39 without cancer) and used to perform a comprehensive analysis. Urine metabolites were extracted using liquid chromatography/mass spectrometry and analysed by Metabolon, Inc. Biomarker candidates were extracted using the Wilcoxon rank sum test, random forest method (RF), and orthogonal partial least squares discriminant analysis (OPLS-DA). RF identified three important metabolic pathways in 15 samples from children with neuroblastoma. One metabolite was selected from each of the three identified pathways and combined to create a biomarker candidate (3-MTS, CTN, and COR) that represented each of the three pathways; using this candidate, all 15 cases were accurately distinguishable from the control group. Two cases in which known biomarkers were negative tested positive using this new biomarker. Furthermore, the predictive value did not decrease in cases with a low therapeutic effect. This approach could be effectively applied to identify biomarkers for other cancer types. |
url |
https://doi.org/10.1038/s41598-021-83619-w |
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