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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-014-0059-9) contains supplementary material, which is available to authorized users.
Highlights
The introduction of prostate specific antigen (PSA) as a biomarker for prostate cancer (PCa) screening and detection has transformed the management of this disease [1,2,3]
The values of area under the curve (AUC) and diagnostics cutoff for serum PSA in the validation set were 0.754 (p = 0.001, 95% CI 0.600-0.907) and 5.50 ng/ml (50.0% specificity, 93.8% sensitivity), respectively
The results indicated that HP/AMBP combination could be potential biomarker set for the diagnosis of PCa with improved accuracy compared to the PSA
Summary
The introduction of prostate specific antigen (PSA) as a biomarker for prostate cancer (PCa) screening and detection has transformed the management of this disease [1,2,3]. Despite the overall success of the PSA blood test, its use has been limited due to the lack of specificity, especially in patients with total serum PSA levels in a range of 2–10 ng/ml Various nonmalignant processes such as benign prostatic hyperplasia (BPH) and prostatitis, as well as manipulation and medical interventions of the prostate lead to serum PSA elevations and subsequently limit the specificity of PSA for cancer detection [4]. The rise of –omics technologies in recent years and their use in PCa research has delivered a number of new potential biomarkers for PCa [6,7,8]. These included proteins, fusing genes, RNA transcripts and epigenetic modifications of DNA. A rich source of potential PCa biomarkers, has the Davalieva et al Proteome Science (2015) 13:2
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