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

Results

General Characteristics

Based on the biopsy results, the 81 participants were subdivided as noncancerous control (BPH) (n = 38), PIN (n = 16), and PCa (n = 27). The range of age was 52 years to 80 years old, and there were no significant differences in the median ages between the groups. The prostate volumes presented medians of 67.5 ml, 56.6 ml, and 45.9 ml across groups, respectively. Prostate volumes were higher (P <.001) in the control group than in the PCa group. Gleason scores available in the PCa group indicative of tumor grade showed that 37% presented a score of ≥7 (Table 1).

Comparisons of Plasma PSA and Plasma Sarcosine Across Groups

PSA levels were higher in the PCa (24.0 ng/mL [6.1–50.4 ng/mL]) than in the control (4.2 ng/mL [2.2–6.6 ng/mL], P <.001) and the PIN (7.7 ng/mL [4.3–10.1 ng/mL], P <.01) groups (Median [25th–75th percentile]). PSA levels were not significantly different between the control and PIN groups (Figure 1A). Plasma sarcosine concentrations were higher in both the PCa (2.0 μM [1.3–3.3 μM], P <.01) and PIN (1.9 μM [1.2–6.5 μM], P <.001) groups than in the control (0.9 μM [0.6–1.4 μM]) group. Plasma sarcosine levels were not significantly different between the PIN and PCa groups (Figure 1B). These comparisons were performed after adjustment for age and prostate volume as covariates.

Figure 1.

Diagnostic performance of total PSA and plasma sarcosine in noncancerous control, PIN and PCa groups. Panels A and B correspond to box plots across groups. Panel C corresponds to ROC curves for PSA and plasma sarcosine to differentiate noncancerous control versus PIN. Panel D corresponds to ROC curves for PSA and plasma sarcosine to differentiate noncancerous control versus PCa. PIN, prostatic intraepithelial neoplasia; PCa, prostate cancer; PSA, prostate-specific antigen; ROC, Receiver Operating Characteristic.

Diagnostic Accuracy Assessment to Differentiate PIN versus Noncancerous Control

ROC curve analyses to assess the diagnostic validity of plasma PSA and plasma sarcosine as differential markers for the presence of PIN versus BPH showed "good" discriminative capability for both plasma PSA (AUC, 0.720) and plasma sarcosine (AUC, 0.734) (Figure 1A and 1B). Plasma PSA presented 69% sensitivity and 64% specificity, and plasma sarcosine presented 75% sensitivity and 72% specificity. Using plasma PSA and plasma sarcosine combined improved the overall diagnostic performance. The diagnostic accuracy for both tests used together was 83%, versus 70% and 77% for PSA and sarcosine when used as single markers, respectively (Table 2).

Diagnostic Accuracy Assessment to Differentiate PCa versus Noncancerous Control

ROC curve analyses to assess the diagnostic validity of plasma PSA and plasma sarcosine as differential markers for the presence of oncological (PCa) versus nononcological prostate gland enlargements (BPH) showed "very good" discriminative capability for both plasma PSA (AUC, 0.854) and plasma sarcosine (AUC, 0.833) (Figure 1C and 1D). Plasma PSA presented 93% sensitivity but only 64% specificity. Plasma sarcosine had 89% sensitivity and 72% specificity. Using plasma PSA and plasma sarcosine combined improved the overall diagnostic performance. The diagnostic accuracy for the two tests used together was 87%, versus 76% and 79% for PSA and sarcosine when used as single markers, respectively (Table 3).

Comparison of PSA and Plasma Sarcosine According to Gleason Score in the PCa Group

Plasma PSA concentrations were significantly (P <.001) different in the group of patients with a Gleason score of <7 (n = 17) versus ≥7 (n = 10). Plasma sarcosine concentrations were not significantly different between the 2 groups (data not shown). Crude and adjusted comparisons had similar statistical differences.

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