Untargeted metabolomics of prostate cancer zwitterionic and positively charged compounds in urine

Cerrato, Andrea; Bedia, Carmen; Capriotti, Anna Laura; Cavaliere, Chiara; Gentile, Vincenzo; Maggi, Martina; Montone, Carmela Maria; Piovesana, Susy; Sciarra, Alessandro; Tauler, Romà; Laganà, Aldo

doi:10.1016/j.aca.2021.338381

Cited by 28 publications

(28 citation statements)

References 64 publications

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“…Among those, metabolomics methods that provide a high-dimensional characterization of low molecular weight biochemicals (metabolites) have shown to be a promising and powerful tool to identify novel PCa biomarkers in biofluids [14][15][16][17][18][19][20][21][22][23]. New advances have been found to describe metabolic alterations that describe tumor growth [24].…”

Section: Introductionmentioning

confidence: 99%

“…Untargeted metabolomics is a "hypothesis-generating discovery strategy" that compares different groups of samples (e.g., cancer vs. controls) [26], which is a promising approach to identify novel metabolic markers. This strategy has been applied recently in PCa [19,27]. Thus, the combination of ultra-high-performance liquid chromatography with high-resolution mass spectrometry (UHPLC-HRMS) and epidemiological approaches may open new perspectives in PCa research, enabling the identification of novel biomarkers for evaluating the future risk of PCa, and the investigation of the etiology of PCa [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

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Plasma Metabolomics for Discovery of Early Metabolic Markers of Prostate Cancer Based on Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry

Lin

Lécuyer

Liu

et al. 2021

Cancers

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Background: The prevention and early screening of PCa is highly dependent on the identification of new biomarkers. In this study, we investigated whether plasma metabolic profiles from healthy males provide novel early biomarkers associated with future risk of PCa. Methods: Using the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, we identified plasma samples collected from 146 PCa cases up to 13 years prior to diagnosis and 272 matched controls. Plasma metabolic profiles were characterized using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) discriminated PCa cases from controls, with a median area under the receiver operating characteristic curve (AU-ROC) of 0.92 using a 1000-time repeated random sub-sampling validation. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) identified the top 10 most important metabolites (p < 0.001) discriminating PCa cases from controls. Among them, phosphate, ethyl oleate, eicosadienoic acid were higher in individuals that developed PCa than in the controls during the follow-up. In contrast, 2-hydroxyadenine, sphinganine, L-glutamic acid, serotonin, 7-keto cholesterol, tiglyl carnitine, and sphingosine were lower. Conclusion: Our results support the dysregulation of amino acids and sphingolipid metabolism during the development of PCa. After validation in an independent cohort, these signatures may promote the development of new prevention and screening strategies to identify males at future risk of PCa.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma Metabolomics for Discovery of Early Metabolic Markers of Prostate Cancer Based on Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry

Lin

Lécuyer

Liu

et al. 2021

Cancers

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“…In order to tailor risk stratification and improve PCa detection, and particularly to reduce unnecessary prostate biopsies and diagnosis of indolent PCa, several tissues based urine and blood tests have been introduced to overcome PSA’s well-known limits [ 7 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Avoiding unnecessary prostate biopsies would allow for a reduction in the risk of side effects inherent to prostate biopsies, as well as associated health costs.…”

Section: Discussionmentioning

confidence: 99%

SelectMDx and Multiparametric Magnetic Resonance Imaging of the Prostate for Men Undergoing Primary Prostate Biopsy: A Prospective Assessment in a Multi-Institutional Study

Maggi

Giudice

Falagario

et al. 2021

Cancers

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Prostate-specific antigen (PSA) testing as the sole indication for prostate biopsy lacks specificity, resulting in overdiagnosis of indolent prostate cancer (PCa) and missing clinically significant PCa (csPCa). SelectMDx is a biomarker-based risk score to assess urinary HOXC6 and DLX1 mRNA expression combined with traditional clinical risk factors. The aim of this prospective multi-institutional study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) when predicting PCa in prostate biopsies. Overall, 310 consecutive subjects were included. All patients underwent mpMRI and SelectMDx prior to prostate biopsy. SelectMDx and mpMRI showed sensitivity and specificity of 86.5% vs. 51.9%, and 73.8% vs. 88.3%, respectively, in predicting PCa at biopsy, and 87.1% vs. 61.3%, and 63.7% vs. 83.9%, respectively, in predicting csPCa at biopsy. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. With analysis of strategies assessed to define the best diagnostic strategy to avoid unnecessary biopsy, SelectMDx appeared to be a reliable pathway after an initial negative mpMRI. Thus, biopsy could be proposed for all cases of mpMRI PI-RADS 4–5 score, and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1–3 score followed by a positive SelectMDx.

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“…Due to the extreme complexity of biological samples, however, several minor compounds are consistently masked by high-abundance species. In a recent paper by Cerrato et al, an untargeted metabolomics study of zwitterionic and positively charged compound was set up thanks to a prior sample pretreatment step [ 68 ]. A cornerstone of any metabolomics study is the acquisition of high-quality data.…”

Section: Role Of Metabolomics In Pc Diagnosismentioning

confidence: 99%

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes

Salciccia

Capriotti

Laganà

et al. 2021

IJMS

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Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.

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Untargeted metabolomics of prostate cancer zwitterionic and positively charged compounds in urine

Cited by 28 publications

References 64 publications

Plasma Metabolomics for Discovery of Early Metabolic Markers of Prostate Cancer Based on Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry

Plasma Metabolomics for Discovery of Early Metabolic Markers of Prostate Cancer Based on Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry

SelectMDx and Multiparametric Magnetic Resonance Imaging of the Prostate for Men Undergoing Primary Prostate Biopsy: A Prospective Assessment in a Multi-Institutional Study

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes

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