Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma

Purpose: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motiv...

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Main Authors: Robert Jirásko, Jakub Idkowiak, Denise Wolrab, Aleš Kvasnička, David Friedecký, Krzysztof Polański, Hana Študentová, Vladimír Študent, Bohuslav Melichar, Michal Holčapek
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/19/4622
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author Robert Jirásko
Jakub Idkowiak
Denise Wolrab
Aleš Kvasnička
David Friedecký
Krzysztof Polański
Hana Študentová
Vladimír Študent
Bohuslav Melichar
Michal Holčapek
author_facet Robert Jirásko
Jakub Idkowiak
Denise Wolrab
Aleš Kvasnička
David Friedecký
Krzysztof Polański
Hana Študentová
Vladimír Študent
Bohuslav Melichar
Michal Holčapek
author_sort Robert Jirásko
collection DOAJ
description Purpose: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motivating us to investigate whether these alterations are reflected in collectible body fluids and whether they can enable RCC detection. Methods: We collected and further analyzed 143 plasma, 100 urine, and 154 tissue samples from 155 kidney cancer patients, together with 207 plasma and 70 urine samples from 214 healthy controls. Results: For the first time, we show elevated concentrations of lactosylsulfatides and decreased levels of sulfatides with hydroxylated fatty acyls in body fluids of RCC patients compared to controls. These alterations are emphasized in patients with the advanced tumor stage. Classification models are able to distinguish between controls and patients with RCC. In the case of all plasma samples, the AUC for the testing set was 0.903 (0.844–0.954), while for urine samples it was 0.867 (0.763–0.953). The models are able to efficiently detect patients with early- and late-stage RCC based on plasma samples as well. The test set sensitivities were 80.6% and 90%, and AUC values were 0.899 (0.832–0.952) and 0.981 (0.956–0.998), respectively. Conclusion: Similar trends in body fluids and tissues indicate that RCC influences lipid metabolism, and highlight the potential of the studied lipids for minimally-invasive cancer detection, including patients with early tumor stages, as demonstrated by the predictive ability of the applied classification models.
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spelling doaj.art-30160943d54746c28f5664c02532d6c32023-11-23T19:53:51ZengMDPI AGCancers2072-66942022-09-011419462210.3390/cancers14194622Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell CarcinomaRobert Jirásko0Jakub Idkowiak1Denise Wolrab2Aleš Kvasnička3David Friedecký4Krzysztof Polański5Hana Študentová6Vladimír Študent7Bohuslav Melichar8Michal Holčapek9Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, 53210 Pardubice, Czech RepublicDepartment of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, 53210 Pardubice, Czech RepublicDepartment of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, 53210 Pardubice, Czech RepublicLaboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacký University, 77900 Olomouc, Czech RepublicLaboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacký University, 77900 Olomouc, Czech RepublicWellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UKDepartment of Oncology, Faculty of Medicine and Dentistry, University Hospital, Palacký University, 77900 Olomouc, Czech RepublicDepartment of Urology, Faculty of Medicine and Dentistry, University Hospital, Palacký University, 77900 Olomouc, Czech RepublicDepartment of Oncology, Faculty of Medicine and Dentistry, University Hospital, Palacký University, 77900 Olomouc, Czech RepublicDepartment of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, 53210 Pardubice, Czech RepublicPurpose: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motivating us to investigate whether these alterations are reflected in collectible body fluids and whether they can enable RCC detection. Methods: We collected and further analyzed 143 plasma, 100 urine, and 154 tissue samples from 155 kidney cancer patients, together with 207 plasma and 70 urine samples from 214 healthy controls. Results: For the first time, we show elevated concentrations of lactosylsulfatides and decreased levels of sulfatides with hydroxylated fatty acyls in body fluids of RCC patients compared to controls. These alterations are emphasized in patients with the advanced tumor stage. Classification models are able to distinguish between controls and patients with RCC. In the case of all plasma samples, the AUC for the testing set was 0.903 (0.844–0.954), while for urine samples it was 0.867 (0.763–0.953). The models are able to efficiently detect patients with early- and late-stage RCC based on plasma samples as well. The test set sensitivities were 80.6% and 90%, and AUC values were 0.899 (0.832–0.952) and 0.981 (0.956–0.998), respectively. Conclusion: Similar trends in body fluids and tissues indicate that RCC influences lipid metabolism, and highlight the potential of the studied lipids for minimally-invasive cancer detection, including patients with early tumor stages, as demonstrated by the predictive ability of the applied classification models.https://www.mdpi.com/2072-6694/14/19/4622cancer biomarkerssulfatidesphingomyelinslipidomicsclassification modelsearly detection
spellingShingle Robert Jirásko
Jakub Idkowiak
Denise Wolrab
Aleš Kvasnička
David Friedecký
Krzysztof Polański
Hana Študentová
Vladimír Študent
Bohuslav Melichar
Michal Holčapek
Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma
Cancers
cancer biomarkers
sulfatide
sphingomyelins
lipidomics
classification models
early detection
title Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma
title_full Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma
title_fullStr Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma
title_full_unstemmed Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma
title_short Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma
title_sort altered plasma urine and tissue profiles of sulfatides and sphingomyelins in patients with renal cell carcinoma
topic cancer biomarkers
sulfatide
sphingomyelins
lipidomics
classification models
early detection
url https://www.mdpi.com/2072-6694/14/19/4622
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