Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer From Benign Prostate Hyperplasia

Pavel A. Markin, MS, PhD(c); Alex Brito, MS, PhD; Natalia Moskaleva, MS, PhD; Miguel Fodor, MD; Ekaterina V. Lartsova, MD; Yevgeny V. Shpot, MD, PhD; Yulia V. Lerner, MD; Vasily Y. Mikhajlov, MD, PhD; Natalia V. Potoldykova, MD; Dimitry V. Enikeev, MD, PhD; Alexey V. Lyundup, PhD; Svetlana A. Appolonova, MS, PhD

Disclosures

Lab Med. 2020;51(6):566-573. 

In This Article

Abstract and Introduction

Abstract

Objective: Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA).

Methods: Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis.

Results: Plasma sarcosine levels were higher in the PCa (2.0 μM [1.3–3.3 μM], P <.01) and the PIN (1.9 μM [1.2–6.5 μM], P <.001) groups than in the BPH (0.9 μM [0.6–1.4 μM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH.

Conclusion: Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.

Introduction

Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death in men.[1] PCa is classified according to the extension of the tumor, the clinical or histopathological stage, and the histopathological grade (Gleason score).[2] The most commonly used tests for screening are the prostate-specific antigen (PSA) test and the digital rectal examination.[2] The incorporation of the PSA test in screening allows for an early diagnosis of asymptomatic individuals with the disease.[2] However, there are issues with the validity of this marker.[3] For example, false-positive and false-negative cases have occurred in patients with tumors with highly undifferentiated histological grade with normal PSA.[3] The discovery of new biomarkers and validation of candidate markers are needed to complement the PSA test and improve diagnosis in clinical practice.[4]

The amino acid sarcosine, also known as N-methylglycine (CH3NHCH2COOH), is an intermediary metabolite in glycine metabolism.[5] High concentrations of sarcosine (ie, sarcosinemia disease) occur in rare genetic abnormalities,[6] but in healthy individuals, sarcosine concentrations are expected to be low or negligible.[7] In 2009, Sreekumar et al. postulated elevated sarcosine concentrations as abnormal in metastatic PCa based on a large metabolomic characterization, with sarcosine a potential biomarker to identify PCa.[8] The diagnostic features of this marker have been studied at different stages of PCa progression, having been measured in urine, serum, plasma, and affected tissues.[8–14] However, there are contradictions in the evidence. The role of sarcosine in carcinogenesis has not been fully understood, and there is no consensus on the use of this marker.[7] Metabolically, the formation of sarcosine is catalyzed by glycine-N-methyltransferase (GNMT). The GNMT gene has been reported to be overexpressed in patients suffering from PCa, and this overexpression has been also associated with an increased risk of the disease.[15,16] Although there has been an interest in studying sarcosine and PCa, there are still unanswered questions and controversies.[8,14,17–21] Most of the studies have been focused on comparing patients with a high severity of PCa versus healthy controls, but they do not take into consideration intermediate stages of PCa, such as prostatic intraepithelial neoplasia (PIN).[8,19–22] Here, we assess the diagnostic performance of plasma sarcosine as a complementary biomarker to the PSA in individuals diagnosed with PIN and with PCa versus individuals diagnosed with benign prostate hyperplasia (BPH) as confirmed by biopsy.

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