Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline

Wang, Sha; Costa, Kerry Ann Da; Fischer, Leslie M.; Milburn, Michael V.; Lawton, Kay A.; Berger, Alvin; Wang, Jia; Zeisel, Steven H.

doi:10.1096/fj.09-154054

Cited by 112 publications

(95 citation statements)

References 73 publications

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“…The present study examined over 500 prostate tissue samples from two independent cohorts of patients, using a state of the art metabolomics platform comprised of UHPLC-MS/MS and GC-MS [27,28]. This study identified biochemical correlates of prostate cancer aggressiveness using a combination of surgical and pathological findings, namely Gleason pattern, extracapsular extension, and spread to seminal vesicles and/or lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

“…Bulk OCT was physically removed from frozen tissue samples and then the samples were prepared for metabolomic characterization as previously described [27,28]. Briefly, tissues were mechanically disaggregated into deionized water at which time a cocktail of recovery standards was added.…”

Section: Metabolomic Prof|lingmentioning

confidence: 99%

“…Since the initial demonstration that sarcosine abundance is associated with prostate cancer aggressiveness, several investigators have worked to determine how best to apply metabolomics in cancer diagnosis and patient management, reviewed in Refs. [41,42].The present study examined over 500 prostate tissue samples from two independent cohorts of patients, using a state of the art metabolomics platform comprised of UHPLC-MS/MS and GC-MS [27,28]. This study identified biochemical correlates of prostate cancer aggressiveness using a combination of surgical and pathological findings, namely Gleason pattern, extracapsular extension, and spread to seminal vesicles and/or lymph nodes.…”

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Metabolomic signatures of aggressive prostate cancer

et al. 2013

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BACKGROUND. Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. METHODS. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. RESULTS. Prostate tumors had significantly altered metabolite profiles compared to cancerfree prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NADþ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). CONCLUSIONS. These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Prostate 73: [1547][1548][1549][1550][1551][1552][1553][1554][1555][1556][1557][1558][1559][1560] 2013. KEY WORDS:clinical heterogeneity; prostate cancer; metabolomics; diagnosis INTRODUCTIONProstate cancer is the most common male malignancy with an estimated 240,000 new cases and more than 28,000 deaths in the United States in 2012 [1]. Clinical detection of prostate cancer increased following the widespread adoption of serum prostate-specific antigen (PSA) screening; however, a significant fraction of prostate cancers detected solely on the basis of an increased serum PSA are indolent. As a result of concerns of over-diagnosis and over-treatment, a new paradigm of active surveillance in patient management has emerged recently [2]. The resulting broad spectrum of treatment options (none, focal therapy, radical surgery, or radiation) has been developed in response to the increased detection of low-risk prostate cancer [3]; however, the current panel of diagnostic tests provides limited information regarding the pr...

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Section: Discussionmentioning

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Section: Metabolomic Prof|lingmentioning

confidence: 99%

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Metabolomic signatures of aggressive prostate cancer

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“…Global untargeted metabolomics utilizing liquid/gas chromatography followed by tandem mass spectrometry was performed as previously described (Metabolon Inc., Morrisville, NC) 24, 25. Briefly, after proteins were precipitated, samples were divided in five fractions for analyses by different mass spectrometry techniques.…”

Section: Methodsmentioning

confidence: 99%

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Nourbakhsh

Bhargava

Tremlett

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo determine if altered tryptophan (Trp) metabolism is associated with MS risk or disease severity in children.MethodsParticipants with pediatric‐onset MS and clinically isolated syndrome (CIS) within 4 years of disease onset and healthy controls underwent collection of serum. Longitudinal disability and processing speed measures and relapse data were collected in cases. Global metabolomics were conducted in 69/67 cases/controls. Targeted Trp measurement was performed in a discovery group (82 cases, 50 controls) and a validation group (92 cases, 50 controls), while functional gut microbiome analysis was done in 17 cases. Adjusted logistic, linear and negative binomial regression and Cox‐proportional hazard models were used.ResultsUsing global metabolomics data, higher relative abundances of Trp and indole lactate, a known gut microbiota‐derived Trp metabolite, were associated with lower risk of MS. In cases, higher relative abundances of gut microbiota‐derived Trp metabolites were associated with lower disability and higher processing speed scores and higher relative abundance of kynurenine was associated with higher relapse rate. Using targeted tryptophan measures, in the discovery and validation groups, each 1 mcg/mL increase in serum Trp level was associated with 20% (95% CI: 4–34%) and 32% (95% CI: 16–44%) decrease in adjusted odds of having MS, respectively. A lower relative abundance of gut microbial genes involved in Trp catabolism was associated with higher relapse risk.InterpretationTrp metabolism by the gut microbiota and the kynurenine pathway may be relevant to the risk of MS in children as well as MS activity and severity.

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“…To remove protein, to dissociate small molecules bound to protein or trapped in the precipitated protein matrix, and to recover chemically diverse metabolites, proteins were precipitated with methanol under vigorous shaking for 2 minutes (Glen Mills Genogrinder 2000), followed by centrifugation. The resulting extract was divided into 5 fractions: one for analysis by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS; positive ionization), one for analysis by UPLC-MS/MS (negative ionization), one for the UPLC-MS/MS polar platform (negative ionization), one for analysis by gas chromatography-mass spectrometry, and one sample was reserved for backup (36,37). Metabolite identification was performed by automated comparison of the ion features in the study samples to a reference library of standard metabolites.…”

Section: Metabolomics Analysismentioning

confidence: 99%