Limits...
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.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.

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

Representative spectra obtained by SELDI-ToF-MS analysis concerning the 4 statistically significant peaks detected with H50 ProteinChip Array.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Representative spectra obtained by SELDI-ToF-MS analysis concerning the 4 statistically significant peaks detected with H50 ProteinChip Array.

Mentions: In summary, SELDI-ToF-MS analysis demonstrated that, in the absence of inflammation, 20 different protein peaks are expressed in PCa in respect to BPH. Of these, only 4 peaks, highlighted in Table 4 (in bold) and shown in Figure 1, could potentially differentiate PCa from BPH, since their expression is not altered by the presence of inflammation. The remaining 16 peaks (also found differentially expressed in presence of inflammation) seem to be strongly related to inflammation, hence they can not be used as markers of PCa (Table 4). The inflammatory process therefore appears to be a limiting factor in the search of biomarkers able to discriminate PCa from BPH and it has not be underrated, since it represents a key mechanism in the development and progression of both diseases [24]. Inflammation is often observed in tumors, with immune cell infiltration and activated stroma. For this reason, cancer patients frequently present changes in various systemic parameters, comprising alterations in the level of serum inflammatory cytokines, acute-phase proteins and total albumin [25]. In fact, inflammation generates not only cancer-promoting microenvironment changes, but also systemic alterations that promote cancer progression [26]. Despite the evidence that inflammation is an intrinsic component of cancer, this fundamental aspect is often ignored in biomarker research studies.


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)

Representative spectra obtained by SELDI-ToF-MS analysis concerning the 4 statistically significant peaks detected with H50 ProteinChip Array.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Representative spectra obtained by SELDI-ToF-MS analysis concerning the 4 statistically significant peaks detected with H50 ProteinChip Array.
Mentions: In summary, SELDI-ToF-MS analysis demonstrated that, in the absence of inflammation, 20 different protein peaks are expressed in PCa in respect to BPH. Of these, only 4 peaks, highlighted in Table 4 (in bold) and shown in Figure 1, could potentially differentiate PCa from BPH, since their expression is not altered by the presence of inflammation. The remaining 16 peaks (also found differentially expressed in presence of inflammation) seem to be strongly related to inflammation, hence they can not be used as markers of PCa (Table 4). The inflammatory process therefore appears to be a limiting factor in the search of biomarkers able to discriminate PCa from BPH and it has not be underrated, since it represents a key mechanism in the development and progression of both diseases [24]. Inflammation is often observed in tumors, with immune cell infiltration and activated stroma. For this reason, cancer patients frequently present changes in various systemic parameters, comprising alterations in the level of serum inflammatory cytokines, acute-phase proteins and total albumin [25]. In fact, inflammation generates not only cancer-promoting microenvironment changes, but also systemic alterations that promote cancer progression [26]. Despite the evidence that inflammation is an intrinsic component of cancer, this fundamental aspect is often ignored in biomarker research studies.

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.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.

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