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.
Highlights
prostate cancer (PCa) is one of the most common non-skin male-related cancers in the world, and it is one of the leading causes of mortality and momentous public health impact in many developed countries, like most western European nations and the United States [1,2]
While prostate specific antigen (PSA) test is a simple and popular test with good sensitivity to detect early cancer; elevated PSA levels had been observed in patients with benign prostatic hyperplasia (BPH) and prostatitis, etc., which means it has a poor specificity towards PCa
Spd, Spm and their corresponding deuterated internal standards were successfully separated and quantified from all samples by UPLC-MS/MS. (Fig 1) The calibration curves were all satisfactory with r2 not less than 0.995 (See S1 Fig), and all Quality control (QC) measures were passed, guaranteeing comparability between samples analyzed on different days
Summary
PCa is one of the most common non-skin male-related cancers in the world, and it is one of the leading causes of mortality and momentous public health impact in many developed countries, like most western European nations and the United States [1,2]. [20] Some studies suggested the role of prostatic Spm concentration as a biomarker for diagnosing PCa owing to the observation of its significantly different levels in non-malignant and malignant tissues. We attempted to evaluate the potential of three main urinary polyamines (Put, Spd and Spm) as biomarkers for PCa detection by comparing the cases between diagnosed PCa, BPH patients and HC.
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