Urinary Polyamines: A Pilot Study on Their Roles as Prostate Cancer Detection Biomarkers

Abstract

Current screening methods towards prostate cancer (PCa) are not without limitations. Research work has been on-going to assess if there are other better tests suitable for primary or secondary screening of PCa to supplement the serum prostate specific antigen (PSA) test, which fails to work accurately in a grey zone of 4-10ng/ml. In this pilot study, the potential roles of urinary polyamines as prostate cancer biomarkers were evaluated. PCa, benign prostatic hyperplasia (BPH) patients and healthy controls (HC) showing PSA>4.0ng/ml were enrolled in the study. Their urine samples were obtained, and the urinary levels of putrescine (Put), spermidine (Spd) and spermine (Spm) were determined by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS). Receiver operating characteristics (ROC) curve and Student's t-test were used to evaluate their diagnostic accuracies. Among the three biogenic polyamines, Spm had demonstrated a good diagnostic performance when comparing their levels in PCa patients with BPH patients (1.47 in PCa vs 5.87 in BPH; p<0.0001). Results are in accordance with transrectal ultrasound prostatic biopsy (TRUSPB) results, with an area under curve (AUC) value of 0.83±0.03. Therefore urinary Spm shows potential to serve as a novel PCa diagnostic biomarker, which in turn can help to address the limited sensitivity and specificity problem of serum PSA test.

Fig 1. Overlaid UPLC-MS/MS SRM chromatograms of 1000 ppb mixed polyamines standard (0–10 mins being shown).

Put (Black peak, t_R = 4.3 min), Put-d₈ (Pink peak, t_R = 4.3 min), Spd (Blue peak, t_R = 6.6 min), Spd-d₈ (Red peak, t_R = 6.6 min), Spm (Yellow peak, t_R = 7.9 min) and Spm-d₈ (Green peak, t_R = 7.9 min).

Fig 2. Distribution of (A) normalized Put, (B) normalized Spd, (C) normalized Spm values in PCa, BPH and HC.

The black bar in the figures indicates the mean value of each subset while the error bar indicates the corresponding SEM.

Fig 3. Receiver operating characteristic analysis for normalized Put, Spd and Spm values.

Fig 4. Polyamine metabolic pathway (focusing on Put, Spd and Spm only).