Sarcosine in Prostate Cancer Tissue is Not a Differential Metabolite for Prostate Cancer Aggressiveness and Biochemical Progression

Jentzmik, Florian; Stephan, Carsten; Lein, Michael; Miller, Kurt; Kamlage, Beate; Bethan, Bianca; Kristiansen, Glen; Jung, Klaus

doi:10.1016/j.juro.2010.09.077

Cited by 80 publications

(64 citation statements)

References 18 publications

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“…13 Moreover, although urinary sarcosine concentrations were higher among prostate cancer cases than in controls in one 14 but not in another validation study, 16 high sarcosine concentration was associated with prostate cancer aggressiveness when measured in prostatic tissue, 15 and with prostate cancer recurrence when measured in serum at prostatectomy. 17 Although the above mentioned observations were based on relatively small and selected study populations, we investigated the role of sarcosine prospectively in a large population-based nested case-control study.…”

Section: Sarcosine and Prostate Cancermentioning

confidence: 82%

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

Vogel

Ulvik

Meyer

et al. 2013

Intl Journal of Cancer

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Methyl group donors and intermediates of one-carbon metabolism affect DNA synthesis and DNA methylation, and may thereby affect prostate carcinogenesis. Choline, the precursor of betaine, and the one-carbon metabolite sarcosine have been associated with increased prostate cancer risk. Within JANUS, a prospective cohort in Norway (n 5 317,000) with baseline serum samples, we conducted a nested case-control study among 3,000 prostate cancer cases and 3,000 controls. Using conditional logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer risk were estimated according to quintiles of circulating betaine, dimethylglycine (DMG), sarcosine, glycine and serine. High sarcosine and glycine concentrations were associated with reduced prostate cancer risk of borderline significance (sarcosine: highest vs. lowest quintile OR 5 0.86, CI 5 0.72-1.01, p trend 5 0.03; glycine: OR 5 0.83, CI 5 0.70-1.00, p trend 5 0.07). Serum betaine, DMG and serine were not associated with prostate cancer risk. However, individuals with a high glycine/serine ratio were at decreased prostate cancer risk (OR 5 0.74, CI 5 0.69-0.85, p trend < 0.001). This population-based study suggested that men with high serum sarcosine or glycine concentrations have modestly reduced prostate cancer risk. Ratios of metabolites reflecting one-carbon balance may be associated with prostate cancer risk, as demonstrated for the glycine/serine ratio, and should be explored in future studies.The folate-mediated one-carbon metabolism, which involves B-vitamins as enzymatic cofactors, is characterized by the transfer of methyl groups and may affect carcinogenesis by influencing methylation and synthesis of DNA.1 Betaine and its precursor choline may act as methyl group sources, 2 whereas intermediates involved in the transfer of one-carbon units may be hypothesized to reflect bioavailability of methyl groups.3 These factors may therefore affect the development and growth of cancer and should be investigated when studying the role of one-carbon metabolism in carcinogenesis. Interestingly, a high S-adenosylmethionine/S-adenosylhomocysteine ratio, which facilitates transmethylation reactions, has been associated with carcinogenesis. 4 Similarly, it may be hypothesized that ratios of one-carbon metabolites, which might reflect one-carbon balance, are related to carcinogenesis.Prostate cancer is the second most frequently diagnosed cancer among men globally. 5 Results from observational studies suggest that high concentrations of circulating folate or high vitamin B12 status are associated with increased prostate cancer risk, although reported associations were modest and sometimes inconsistent.6-8 Although increased prostate cancer risk was suggested in one trial among subjects receiving folic acid supplements, 9 recent meta-analyses did not suggest an association with increased prostate cancer risk. 10,11 Nevertheless, an observational population-based study previously showed

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Section: Sarcosine and Prostate Cancermentioning

confidence: 82%

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

Vogel

Ulvik

Meyer

et al. 2013

Intl Journal of Cancer

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“…Since sarcosine was originally shown to be a mechanistic biomarker of aggressive prostate cancer, there has been critical discussion in the literature regarding the clinical utility of this metabolite. Most studies have demonstrated that post-DRE urine sarcosine measurements are predictive of prostate cancer [11][12][13]; however, the findings in serum and tissue are more controversial [14][15][16][17]. As Issaq and Veenstra [18] pointed out, the results of these studies may not be directly comparable due to methodologic differences in sarcosine measurement.…”

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confidence: 99%

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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“…Their conclusion was similar to that of Jentzmik et al [7] that ''serum sarcosine is not a marker for prostate cancer''. Later on Jentzmik et al [12] published another study measuring the levels of sarcosine by GC/MS in matched malignant and non-malignant tissue samples from 92 patients with prostate cancer. Again they concluded that prostate cancer tissue levels of sarcosine do not differ from nonmalignant tissue, obviating the use of this metabolite as a biomarker for prostate cancer aggressiveness and biochemical progression.…”

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confidence: 99%

Is sarcosine a biomarker for prostate cancer?

Issaq¹,

Veenstra²

2011

J of Separation Science

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Sarcosine in Prostate Cancer Tissue is Not a Differential Metabolite for Prostate Cancer Aggressiveness and Biochemical Progression

Abstract: Sarcosine in prostate cancer tissue samples cannot be considered a suitable predictor of tumor aggressiveness or biochemical recurrence.

Cited by 80 publications

References 18 publications

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

Metabolomic signatures of aggressive prostate cancer

Is sarcosine a biomarker for prostate cancer?

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