RESUMO
Currently used tumor markers for early diagnosis of prostate cancer (PCa) are often lacking sufficient specificity and sensitivity. Therefore, the diagnostic potential of selected microRNAs in comparison to serum PSA levels and PSA density (PSAD) was explored. A panel of 12 PCa-associated microRNAs was quantified by qPCR in urinary sediments from 50 patients with suspected PCa undergoing prostate biopsy, whereupon PCa was detected in 26 patients. Receiver operating characteristic (ROC) curve analyses revealed a potential for non-invasive urine-based PCa detection for miR-16 (AUC = 0.744, p = 0.012; accuracy = 76%) and miR-195 (AUC = 0.729, p = 0.017; accuracy = 70%). While serum PSA showed an insufficient diagnostic value (AUC = 0.564, p = 0.656; accuracy = 50%) in the present cohort, PSAD displayed an adequate diagnostic performance (AUC = 0.708, p = 0.031; accuracy = 70%). Noteworthy, the combination of PSAD with the best candidates miR-16 and miR-195 either individually or simultaneously improved the diagnostic power (AUC = 0.801-0.849, p < 0.05; accuracy = 76-90%). In the sub-group of patients with PSA ≤ 10 ng/mL (n = 34), an inadequate diagnostic power of PSAD alone (AUC = 0.595, p = 0.524; accuracy = 68%) was markedly surpassed by miR-16 and miR-195 individually as well as by their combination with PSAD (AUC = 0.772-0.882, p < 0.05; accuracy = 74-85%). These findings further highlight the potential of urinary microRNAs as molecular markers with high clinical performance. Overall, these results need to be validated in a larger patient cohort.
RESUMO
OBJECTIVES: To examine erythrocyte band III transport protein (SLC4A1), erythrocyte oxalate flux, and plasmatic, cellular, and urine oxalate concentrations and blood gas analyses in calcium oxalate monohydrate stone-forming patients (COM) in comparison with normal controls (NC). METHODS: Isolated red cells from 51 NC and 25 COM cases were divided for cellular oxalate measurement and for measurement of transcellular erythrocyte oxalate flux (pH 7.48-8.24). SLC4A1 protein levels were determined by Western blot analyses. Plasmatic and urinary oxalate levels and the venous blood gas analysis were measured simultaneously. RESULTS: SLC4A1 protein levels were significantly higher in COM (8.76 ± 2.12) than in NC (4.17 ± 0.61; P < .02). Cellular oxalate and venous HCO(3)(-) were significantly lower in COM (2.35 ± 0.26 µmol/L) and (24.06 ± 0.24 mmo/l) than in NC (4.03 ± 0.49 µmol/L; P < .05) and (24.93 ± 0.17 mmol/L; P < .01). Urinary oxalate was significantly higher in COM (0.31 ± 0.02 mmol/L) than in NC (0.25 ± 0.01 mmol/L; P < .04). The erythrocyte transmembrane oxalate flux correlated with the pH value and with the urinary oxalate in both groups (r = .25-.55; P = .01). With increased pH values, the oxalate flux showed inverse effects in both groups. CONCLUSIONS: SLC4A1 associated changes of HCO(3)(-) and pH levels influenced the cellular oxalate levels and urinary oxalate clearance. Under normal conditions (pH 7.55) the oxalate efflux in COM was comparable with the acid stimulated oxalate efflux in NC. The addition of HCO(3)(-) compensated the flux of COM stone formers to the levels of normal controls.
