Abstract
BackgroundA more specific and early diagnostics for prostate cancer (PCa) is highly desirable. In this study, being inflammation the focus of our effort, serum protein profiles were analyzed in order to investigate if this parameter could interfere with the search of discriminating proteins between PCa and benign prostatic hyperplasia (BPH).MethodsPatients with clinical suspect of PCa and candidates for trans-rectal ultrasound guided prostate biopsy (TRUS) were enrolled. Histological specimens were examined in order to grade and classify the tumor, identify BPH and detect inflammation. Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-ToF-MS) and two-dimensional gel electrophoresis (2-DE) coupled with Liquid Chromatography-MS/MS (LC-MS/MS) were used to analyze immuno-depleted serum samples from patients with PCa and BPH.ResultsThe comparison between PCa (with and without inflammation) and BPH (with and without inflammation) serum samples by SELDI-ToF-MS analysis did not show differences in protein expression, while changes were only observed when the concomitant presence of inflammation was taken into consideration. In fact, when samples with histological sign of inflammation were excluded, 20 significantly different protein peaks were detected. Subsequent comparisons (PCa with inflammation vs PCa without inflammation, and BPH with inflammation vs BPH without inflammation) showed that 16 proteins appeared to be modified in the presence of inflammation, while 4 protein peaks were not modified. With 2-DE analysis, comparing PCa without inflammation vs PCa with inflammation, and BPH without inflammation vs the same condition in the presence of inflammation, were identified 29 and 25 differentially expressed protein spots, respectively. Excluding samples with inflammation the comparison between PCa vs BPH showed 9 unique PCa proteins, 4 of which overlapped with those previously identified in the presence of inflammation, while other 2 were new proteins, not identified in our previous comparisons.ConclusionsThe present study indicates that inflammation might be a confounding parameter during the proteomic research of candidate biomarkers of PCa. These results indicate that some possible biomarker-candidate proteins are strongly influenced by the presence of inflammation, hence only a well-selected protein pattern should be considered for potential marker of PCa.
Highlights
A more specific and early diagnostics for prostate cancer (PCa) is highly desirable
Cancer survival rates depend on the early detection of the disease: currently, PCa diagnosis is performed using digital rectal exploration (DRE), trans-rectal ultrasound guided prostate biopsy (TRUS), and by the measurement of serum prostate-specific antigen (PSA) levels
PSA is a sensitive marker for the detection of PCa, it is not cancer-specific; elevated serum PSA levels are observed in benign enlargements of the prostate, such as benign prostatic hyperplasia (BPH) or prostatitis, and after biopsy [22]
Summary
A more specific and early diagnostics for prostate cancer (PCa) is highly desirable. In this study, being inflammation the focus of our effort, serum protein profiles were analyzed in order to investigate if this parameter could interfere with the search of discriminating proteins between PCa and benign prostatic hyperplasia (BPH). The serum marker currently used for the diagnosis of PCa is the prostate-specific antigen (PSA), which is not reliable, having a predictive value estimated at 25%-35% in the range of 2.6 – 10 ng/mL [2] Benign conditions such as prostatitis and benign prostatic hyperplasia (BPH) can lead to an increase in PSA levels causing false positive [5,6]. Ornstein et al reported serum proteomic patterns obtained by Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-ToF-MS) analysis to discriminate PCa from BPH when PSA level is between 2.5 and 15 ng/mL, with the aim to decrease unnecessary prostate biopsies [16]. Ummanni et al examined biopsy samples from BPH and PCa patients using two-dimensional gel electrophoresis (2-DE) followed by Matrix Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry analysis (MALDI-ToF-MS), to identify potential biomarkers that might differentiate the two clinical events [17]
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