title: Proteomics analysis of urine reveals acute phase response proteins as candidate diagnostic biomarkers for prostate cancer.
abstract: Despite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p < 0.05), 1.8 fold variation or more in abundance, showed 41 spots, corresponding to 23 proteins. The Ingenuity Pathway Analysis showed significant association with the Acute Phase Response Signaling pathway. Nine proteins with differential abundances were included in this pathway: AMBP, APOA1, FGA, FGG, HP, ITIH4, SERPINA1, TF and TTR. The expression pattern of 4 acute phase response proteins differed from the defined expression in the canonical pathway. The urine levels of TF, AMPB and HP were measured by immunoturbidimetry in an independent validation set. The concentration of AMPB in urine was significantly higher in PCa while levels of TF and HP were opposite (p < 0.05). The AUC for the individual proteins ranged from 0.723 to 0.754. The combination of HP and AMBP yielded the highest accuracy (AUC = 0.848), greater than PSA. The proposed biomarker set is quickly quantifiable and economical with potential to improve the sensitivity and specificity of PCa detection.
authors: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Krste Misirkov 2, 1000 Skopje, Republic of Macedonia.
authors: Katarina
authors: K
authors: Davalieva
authors: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Krste Misirkov 2, 1000 Skopje, Republic of Macedonia.
authors: Sanja
authors: S
authors: Kiprijanovska
authors: Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of Macedonia.
authors: Selim
authors: S
authors: Komina
authors: Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of Macedonia.
authors: Gordana
authors: G
authors: Petrusevska
authors: Biochemical laboratory, Clinical Hospital "Acibadem Sistina", Skopje, Republic of Macedonia.
authors: Natasha Chokrevska
authors: NC
authors: Zografska
authors: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Krste Misirkov 2, 1000 Skopje, Republic of Macedonia.
authors: Momir
authors: M
authors: Polenakovic
keywords: 2-D DIGE; Benign prostate hyperplasia; MS; Non-invasive biomarkers; Prostate cancer; Urine analysis
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