Thiol Groups as a Biomarker for the Diagnosis and Prognosis of Prostate Cancer

Abstract

Oxidative stress (OS) is associated with the onset of prostate cancer (PCa). The aims of this study are to examine whether OS biomarkers may be employed as external validating criteria for the diagnosis PCa. This case-control study recruited 204 subjects, 73 patients with PCa, 67 patients with benign prostate hyperplasia (BPH), and 64 healthy controls (HC) and assayed plasma prostate-specific antigen (PSA), protein thiol (-SH) groups, lipid hydroperoxides, carbonyl proteins (PCB), advanced oxidation protein products (AOPP), and total radical-trapping antioxidant parameter (TRAP). -SH groups were significantly and inversely associated with PSA levels. PCa was characterized by lowered -SH groups and red blood cell TRAP levels, and higher PSA, AOPP and PCB levels as compared with BPH and HC. Support vector machine with 10-fold cross-validation showed that PSA values together with -SH groups, PCB and AOPP yielded a cross-validation accuracy of 96.34% for the differentiation of PCa from BPH and HC. The area under the ROC curve using PSA and -SH differentiating PCa from BPH and controls was 0.945. Moreover, lowered -SH, but not PSA, are associated with PCa metastasis and progression. Inflammatory biomarkers were not associated with PCa or BPH. PCa, its progression and metastatic PCa are characterized by lowered antioxidant defenses, especially lowered thiol groups, and increased oxidative stress toxicity, suggesting that these processes play a key role in the pathophysiology of PCa. An algorithm based on -SH and PSA values may be used to differentiate patients with PCa from those with BPH and controls.

Figure 1

Correlation between total prostate-specific antigen (PSA) and thiol (−SH) groups.

Figure 2

Total and free PSA levels and oxidative stress biomarkers (all in z values) in healthy controls (HC), patients with Benign Prostate Hyperplasia (BPH), and prostate cancer (PCa). PSA: prostate-specific antigen. -SH: thiol. AOPP: advanced oxidized protein products. PCB: protein carbonyls. LOOH RBC: lipid hydroperoxides in red blood cells. TRAP: total radical-trapping antioxidant parameter.

Figure 3

Differences in total PSA and oxidative stress biomarkers between patients with prostate cancer metastasis (metastatic PCa) versus patients without metastasis (No). PSA: prostate-specific antigen. SH: thiol. AOPP: advanced oxidized protein products. PCB: protein carbonyls. LOOH RBC: lipid hydroperoxides in red blood cells. CRP: high sensitivity C-reactive protein. WBC: white blood cells. ESR: erythrocyte sedimentation rate. Hb: hemoglobin.

Figure 4

shows the biomarkers in those with a suspicious digital rectal examination versus a normal examination (See Fig. 3 for abbrevations).

Figure 5

Shows that AV group 3 (risk group3) is characterized by lowered -SH group values (F = 8.91, df = 1/60, p = 0.004) and higher ESR (F = 9.03, df = 1/60, p = 0.004) than AV groups 1 + 2 (See Fig. 3 for abbreviations).