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Inflammation: an important parameter in the search of prostate cancer biomarkers.

Bergamini S, Bellei E, Reggiani Bonetti L, Monari E, Cuoghi A, Borelli F, Sighinolfi MC, Bianchi G, Ozben T, Tomasi A - Proteome Sci (2014)

Bottom Line: The 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.The present study indicates that inflammation might be a confounding parameter during the proteomic research of candidate biomarkers of PCa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Diagnostic Medicine, Clinic and Public Health, Proteomic Lab, University Hospital of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.

ABSTRACT

Background: 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).

Methods: Patients 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.

Results: The 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus

Bi-dimensional proteome maps of serum samples from PCa without (A) and with inflammation (B), and BPH in absence (C) and presence of inflammation (D). Proteins were resolved by IEF over the pH range 4–7, followed by 8-16% gradient gel and visualized by Silver staining. Significant differentially expressed proteins are marked with alphanumeric labels, corresponding to those listed in Tables 5, 6 and 7. Yellow tags indicate the overlapped proteins detected in presence of inflammation in both PCa (B) and BPH (D) conditions. Some of these proteins were also revealed in PCa in absence of inflammation (A, third comparison). Additionally, in this latter situation, green labels represent proteins not previously identified in the first and second comparisons, namely in presence of inflammation.
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Figure 2: Bi-dimensional proteome maps of serum samples from PCa without (A) and with inflammation (B), and BPH in absence (C) and presence of inflammation (D). Proteins were resolved by IEF over the pH range 4–7, followed by 8-16% gradient gel and visualized by Silver staining. Significant differentially expressed proteins are marked with alphanumeric labels, corresponding to those listed in Tables 5, 6 and 7. Yellow tags indicate the overlapped proteins detected in presence of inflammation in both PCa (B) and BPH (D) conditions. Some of these proteins were also revealed in PCa in absence of inflammation (A, third comparison). Additionally, in this latter situation, green labels represent proteins not previously identified in the first and second comparisons, namely in presence of inflammation.

Mentions: Representative 2-D gels obtained from depleted serum samples are reported in Figure 2. Inflammation-free PCa vs PCa with inflammation were first compared (first comparison); then, BPH was considered in the absence or presence of inflammation (second comparison), and finally the two conditions were compared with the exclusion of inflammation (third comparison). The differentially expressed protein spots are marked in the images by alphanumeric labels, that correspond to those reported in the first column of Tables 5, 6 and 7, respectively. The second column of Tables 5, 6 and 7 refers to the primary accession number, derived from the UniProt knowledge database, the third column provides the complete name of each identified protein and column 4 reports the theoretical molecular weight (MW). Column 5 shows the highest ion scores obtained with MASCOT search engine, expressed as the probability that the observed match between the experimental data and the database sequence could be due to a random event. Column 6 indicates the total number of peptides that matched the identified proteins and the significant matches, while column 7 reports the total number of sequences and the number of significant sequences. Finally, the last column reports the protein expression change, indicated by arrows.


Inflammation: an important parameter in the search of prostate cancer biomarkers.

Bergamini S, Bellei E, Reggiani Bonetti L, Monari E, Cuoghi A, Borelli F, Sighinolfi MC, Bianchi G, Ozben T, Tomasi A - Proteome Sci (2014)

Bi-dimensional proteome maps of serum samples from PCa without (A) and with inflammation (B), and BPH in absence (C) and presence of inflammation (D). Proteins were resolved by IEF over the pH range 4–7, followed by 8-16% gradient gel and visualized by Silver staining. Significant differentially expressed proteins are marked with alphanumeric labels, corresponding to those listed in Tables 5, 6 and 7. Yellow tags indicate the overlapped proteins detected in presence of inflammation in both PCa (B) and BPH (D) conditions. Some of these proteins were also revealed in PCa in absence of inflammation (A, third comparison). Additionally, in this latter situation, green labels represent proteins not previously identified in the first and second comparisons, namely in presence of inflammation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4061775&req=5

Figure 2: Bi-dimensional proteome maps of serum samples from PCa without (A) and with inflammation (B), and BPH in absence (C) and presence of inflammation (D). Proteins were resolved by IEF over the pH range 4–7, followed by 8-16% gradient gel and visualized by Silver staining. Significant differentially expressed proteins are marked with alphanumeric labels, corresponding to those listed in Tables 5, 6 and 7. Yellow tags indicate the overlapped proteins detected in presence of inflammation in both PCa (B) and BPH (D) conditions. Some of these proteins were also revealed in PCa in absence of inflammation (A, third comparison). Additionally, in this latter situation, green labels represent proteins not previously identified in the first and second comparisons, namely in presence of inflammation.
Mentions: Representative 2-D gels obtained from depleted serum samples are reported in Figure 2. Inflammation-free PCa vs PCa with inflammation were first compared (first comparison); then, BPH was considered in the absence or presence of inflammation (second comparison), and finally the two conditions were compared with the exclusion of inflammation (third comparison). The differentially expressed protein spots are marked in the images by alphanumeric labels, that correspond to those reported in the first column of Tables 5, 6 and 7, respectively. The second column of Tables 5, 6 and 7 refers to the primary accession number, derived from the UniProt knowledge database, the third column provides the complete name of each identified protein and column 4 reports the theoretical molecular weight (MW). Column 5 shows the highest ion scores obtained with MASCOT search engine, expressed as the probability that the observed match between the experimental data and the database sequence could be due to a random event. Column 6 indicates the total number of peptides that matched the identified proteins and the significant matches, while column 7 reports the total number of sequences and the number of significant sequences. Finally, the last column reports the protein expression change, indicated by arrows.

Bottom Line: The 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.The present study indicates that inflammation might be a confounding parameter during the proteomic research of candidate biomarkers of PCa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Diagnostic Medicine, Clinic and Public Health, Proteomic Lab, University Hospital of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.

ABSTRACT

Background: 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).

Methods: Patients 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.

Results: The 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus