Scientific African (Sep 2022)
Diagnostic potential value of circulating PCA3 mRNA in plasma and urine of prostate cancer patients
Abstract
Current reports show that most of the routinely available prostate specific antigen (PSA) derived biomarkers of prostate cancer (PCa) have failed to demonstrate sufficient sensitivity and specificity in clinical use for diagnosis and prognosis of PCa. Consequently, a number of molecular markers including the prostate cancer gene 3 (PCA3) are being considered for clinical use. This study was therefore designed to determine the levels of PCA3 mRNA expression in urine and plasma of prostate cancer patients and to assess its diagnostic characteristics in Nigerian population with prostate cancer. A total of 90 participants comprising 30 participants each with PCa, BPH and 30 apparently healthy adults as controls were enrolled into this case-control study. Blood and urine samples were collected from study participants and dispensed into PaxGene RNA protecting fluid, lithium heparin bottles and nuclease free bottle as appropriate. Anthropometric indices were obtained using standard methods, while the plasma levels of PSA, testosterone and estrogen were determined using enzyme linked immunosorbent assay (ELISA). The PCA3 mRNA expression in urine and plasma was determined using Quantitative Polymerase Chain Reaction. Comparison of groups was done using analysis of variance (ANOVA) followed by Tukey Post-Hoc test. The sensitivity and specificity of PCA3 mRNA in the diagnosis of PCa was evaluated through estimation of the area under the receiver operating characteristic (ROC) curve. 'The mean waist circumference (WC) and (HC) was significantly higher in the BPH group (43.94 ± 2.32) compared to both the control (36.04 ± 0.80) and the PCa group (38.50 ± 0.94) (p < 0.05). The prostate cancer group had a significantly higher levels (p < 0.05) of tPSA (47.58 ± 12.23) and an increased expression of PCA3 mRNA in urine (10.46 ± 1.68) and plasma (14.89 ± 1.37) when compared with control values [tPSA (0.67 ± 0.27), urine (2.22 ± 0.22) and plasma (1.45 ± 0.13) expression of PCA3 mRNA]. A negative correlation was found to exist between Plasma PCa3 mRNA and plasma levels of estradiol (r=-0.425, p = 0.024) and testosterone (r=-0.423, p = 0.025) in PCa group. A similar trend was observed between urine PCA3 mRNA, estrogen (r=-0.459, p = 0.014) and testosterone (r=-0.407, p = 0.031). The ROC curve shows the tPSA (p = 0.03) is the most sensitive marker of detection followed by plasma PCA3 mRNA and subsequently the urine PCA3 mRNA. The curve further shows the urine PCA3 mRNA (p = 0.006) is the most specific for detection of prostate cancer and the less and least sensitive are the plasma PCA3 mRNA and tPSA. It could be concluded from this study that there is reduced levels of estradiol and testosterone and elevated levels of tPSA and PCA3 mRNA expression in urine and blood in patients with benign prostatic hyperplasia and prostate cancer. Hence, determination of plasma or urine expression of PCA3 mRNA is valueable in the diagnosis and treatment monitoring of prostate cancer.
