Urinary acylcarnitines are altered in human kidney cancer

Ganti, Sheila; Taylor, Sandra L.; Kim, Kyoungmi; Hoppel, Charles L.; Guo, Lining; Yang, Joy C.; Evans, Christopher P.; Weiss, Robert H.

doi:10.1002/ijc.26274

Cited by 127 publications

(97 citation statements)

References 28 publications

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“…Metabolomic profiling was performed as described previously for the analysis of saliva, plasma, and urine [19][20][21]. For all matrices, samples from the three consumer groups were extracted and split into equal parts for analysis on gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry/mass spectrometry platforms [22].…”

Section: Metabolomic Profiling Technologymentioning

confidence: 99%

Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

Prasad¹,

Jones²,

Schmidt³

et al. 2015

J Metabolomics

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Background: The existing US epidemiological data show that long-term cigarette smokers are at higher risk of developing serious diseases relative to moist snuff consumers. To understand the effects of tobacco consumption, global metabolomic profiles were generated. Here, we describe metabolomic changes in oxidative stress and inflammation pathways. Methods: Matching plasma, urine, and saliva samples from chronic/long-term smokers (SMK), moist snuff consumers (MSC), and non-tobacco consumers (NTC), 40 subjects in each cohort, were collected in a crosssectional biomarker discovery study. Untargeted metabolomics and data analyses were performed using Metabolon's proprietary technology. Results: Several biochemicals that significantly differed between study cohorts were identified in all three matrices, with most metabolites found in urine. Random forest analyses of the metabolomes grouped study subjects with a high accuracy and indicated that nicotine and its metabolites primarily drive separation between the NTC and MSC; otherwise, metabolomic profiles of NTC and MSC are more similar to each other, and SMK appear to manifest a distinct metabolomic profile. SMK exhibit lower levels of antioxidants, changes in glutathione metabolism and purine degradation pathways, docosahexaenoate, arachidonate, and 12-hydroxyeicosatetraenoic acid, suggesting increased oxidative stress and inflammation relative to MSC and NTC. Conclusions: Metabolomic profiles show that while SMK and MSC cohorts exhibit higher levels of nicotine and its metabolites, SMK manifest evidence of increased oxidative stress and inflammation relative to MSC and NTC. These observed biochemical changes in the SMK could be likely due to the combustion-related toxicants present in cigarette smoke. Impact: Several differentiating metabolites identified herein could be utilized as potential biomarkers of effect. Further, the metabolomic profiles improve our understanding of biological changes in tobacco consumers.

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Section: Metabolomic Profiling Technologymentioning

confidence: 99%

Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

Prasad¹,

Jones²,

Schmidt³

et al. 2015

J Metabolomics

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“…3 To this day, we use targeted metabolomics whenever we use a urinary dipstick at the bedside or clinical laboratory. More recently, yet prior to its current appellation, metabolomics-type evaluations of both plasma cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades, 18 suggesting involvement of fatty acid oxidation in RCC energy metabolism. In addition to biomarker studies, a human RCC to mouse xenograft metabolomics study of urine, blood, and malignant tissues resulted in identification of several novel therapeutic targets by showing that there exists alteration of metabolites in tryptophan, peroxisome proliferator-activated receptor α (PPARα), and fatty acid oxidation pathways; 17 these targets are currently being validated in our laboratory with initially promising results.…”

Section: Techniques Of Metabolomics Analysismentioning

confidence: 99%

Applications of Metabolomics for Kidney Disease Research

Wettersten

Weiss

2013

Organogenesis

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Metabolomics is one of the relative newcomers of the omics techniques and is likely the one most closely related to actual real-time disease pathophysiology. Hence, it has the power to yield not only specific biomarkers but also insight into the pathophysiology of disease. Despite this power, metabolomics as applied to kidney disease is still in its early adolescence and has not yet reached the mature stage of clinical application, i.e., specific biomarker and therapeutic target discovery. On the other hand, the insight gained from hints into what makes these diseases tick, as is evident from the metabolomics pathways which have been found to be altered in kidney cancer, are now beginning to bear fruit in leading to potential therapeutic targets. It is quite likely that, with greater numbers of clinical materials and with more investigators jumping into the field, metabolomics may well change the course of kidney disease research.

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“…Urine analysis in individuals with RCC identified quinolinate, 4-hydroxybenzoate, and gentisate, which are involved in pathways of amino acid and energetic metabolism, consistent with cancers exhibiting a Warburg phenotype (79). The detection of acylcarnitines in the urine during a separate study suggested a biomarker of advanced RCC (47). The role of NOX oxidases, upstream or downstream, of cancer metabolism has not been studied, but it is an active area of investigation in our laboratory.…”

Section: Metabolomicsmentioning

confidence: 94%

Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved

Shanmugasundaram

Block

2016

Antioxidants & Redox Signaling

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Significance: The number of kidney cancers is growing 3-5% each year due to unknown etiologies. Intra-and inter-tumor mediators increase oxidative stress and drive tumor heterogeneity. Recent Advances: Technology advancement in state-of-the-art instrumentation and methodologies allows researchers to detect and characterize global landscaping modifications in genes, proteins, and pathophysiology patterns at the single-cell level. Critical Issues: We postulate that the sources of reactive oxygen species (ROS) and their activation within subcellular compartments will change over a timeline of tumor evolvement and contribute to tumor heterogeneity. Therefore, the complexity of intracellular changes within a tumor and ROS-induced tumor heterogeneity coupled to the advancement of detecting these events globally are limited at the level of data collection, organization, and interpretation using software algorithms and bioinformatics. Future Directions: Integrative and collaborative research, combining the power of numbers with careful experimental design, protocol development, and data interpretation, will translate cancer biology and therapeutics to a heightened level or leave the abundant raw data as stagnant and underutilized. Antioxid. Redox Signal. 25, 685-701.

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Urinary acylcarnitines are altered in human kidney cancer

Cited by 127 publications

References 28 publications

Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

Applications of Metabolomics for Kidney Disease Research

Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved

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