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Mass spectrometry-based analysis of therapy-related changes in serum proteome patterns of patients with early-stage breast cancer.

Pietrowska M, Polanska J, Marczak L, Behrendt K, Nowicka E, Stobiecki M, Polanski A, Tarnawski R, Widlak P - J Transl Med (2010)

Bottom Line: On the other hand, significant long-term effects were observed in serum proteome patterns one year after the end of basic treatment (we found that about 20 peptides exhibited significant changes in their abundances).Moreover, the significant differences were found primarily in the subgroup of patients treated with adjuvant therapy, but not in the subgroup subjected only to surgery.On the other hand, no significant correlation was found between changes in the abundance of any spectral component or clinical features of patients, including staging and grading of tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.

ABSTRACT

Background: The proteomics approach termed proteome pattern analysis has been shown previously to have potential in the detection and classification of breast cancer. Here we aimed to identify changes in serum proteome patterns related to therapy of breast cancer patients.

Methods: Blood samples were collected before the start of therapy, after the surgical resection of tumors and one year after the end of therapy in a group of 70 patients diagnosed at early stages of the disease. Patients were treated with surgery either independently (26) or in combination with neoadjuvant chemotherapy (5) or adjuvant radio/chemotherapy (39). The low-molecular-weight fraction of serum proteome was examined using MALDI-ToF mass spectrometry, and then changes in intensities of peptide ions registered in a mass range between 2,000 and 14,000 Da were identified and correlated with clinical data.

Results: We found that surgical resection of tumors did not have an immediate effect on the mass profiles of the serum proteome. On the other hand, significant long-term effects were observed in serum proteome patterns one year after the end of basic treatment (we found that about 20 peptides exhibited significant changes in their abundances). Moreover, the significant differences were found primarily in the subgroup of patients treated with adjuvant therapy, but not in the subgroup subjected only to surgery. This suggests that the observed changes reflect overall responses of the patients to the toxic effects of adjuvant radio/chemotherapy. In line with this hypothesis we detected two serum peptides (registered m/z values 2,184 and 5,403 Da) whose changes correlated significantly with the type of treatment employed (their abundances decreased after adjuvant therapy, but increased in patients treated only with surgery). On the other hand, no significant correlation was found between changes in the abundance of any spectral component or clinical features of patients, including staging and grading of tumors.

Conclusions: The study establishes a high potential of MALDI-ToF-based analyses for the detection of dynamic changes in the serum proteome related to therapy of breast cancer patients, which revealed the potential applicability of serum proteome patterns analyses in monitoring the toxicity of therapy.

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Related in: MedlinePlus

Changes in serum proteome patterns specific for subgroups of patients. A - Analysis of the group of patients subjected to surgery and adjuvant therapy. B - Analysis of the group of patients subjected only to surgery. Left - the q-values are plotted against the p-values of differences between samples B and C; each dot represents one spectral component, the red horizontal line represents a q-value cut-off equal to 0.1. Right - average differential spectra for samples B and C.
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Figure 2: Changes in serum proteome patterns specific for subgroups of patients. A - Analysis of the group of patients subjected to surgery and adjuvant therapy. B - Analysis of the group of patients subjected only to surgery. Left - the q-values are plotted against the p-values of differences between samples B and C; each dot represents one spectral component, the red horizontal line represents a q-value cut-off equal to 0.1. Right - average differential spectra for samples B and C.

Mentions: In order to test the hypothesis that observed differences were related to adjuvant radio/chemotherapy two subgroups of patients were analyzed in parallel: patients subjected only to surgery (26 persons) and patients treated with adjuvant therapy (39 persons). As expected, in neither subgroup significant differences between samples A and B were found. Surprisingly, also when samples A and C were compared differences for none of spectral components reached the level of statistical significance (q < 0.1) in both groups of patients, which apparently was related to smaller numbers of samples in these subgroups. However, clear differences were observed between two groups of patients when samples B and C were compared. Several spectral components changed their abundance significantly between these two time points when samples from patients subjected to adjuvant therapy were analyzed. The q-value of the difference in abundance of 26 spectral components reached the level of <0.1 when serum samples from this subgroup were analyzed (Figure 2A). In marked contrast, none of spectral components changed their abundance significantly between time points B and C when samples of patients subjected only to surgery were analyzed (Figure 2B). Noteworthy, 16 out of 26 spectral components that differentiated samples B and C in the subgroup subjected to adjuvant therapy also differentiated samples B and C when the group of whole patients were analyzed (at the level of q-value < 0.1; Table 1). We conclude that differences in serum proteome patterns observed between samples collected after the surgery and one year after the end of basic therapy were specific for the group of patients subjected to adjuvant therapy, and this reflects changes related to this treatment.


Mass spectrometry-based analysis of therapy-related changes in serum proteome patterns of patients with early-stage breast cancer.

Pietrowska M, Polanska J, Marczak L, Behrendt K, Nowicka E, Stobiecki M, Polanski A, Tarnawski R, Widlak P - J Transl Med (2010)

Changes in serum proteome patterns specific for subgroups of patients. A - Analysis of the group of patients subjected to surgery and adjuvant therapy. B - Analysis of the group of patients subjected only to surgery. Left - the q-values are plotted against the p-values of differences between samples B and C; each dot represents one spectral component, the red horizontal line represents a q-value cut-off equal to 0.1. Right - average differential spectra for samples B and C.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2908576&req=5

Figure 2: Changes in serum proteome patterns specific for subgroups of patients. A - Analysis of the group of patients subjected to surgery and adjuvant therapy. B - Analysis of the group of patients subjected only to surgery. Left - the q-values are plotted against the p-values of differences between samples B and C; each dot represents one spectral component, the red horizontal line represents a q-value cut-off equal to 0.1. Right - average differential spectra for samples B and C.
Mentions: In order to test the hypothesis that observed differences were related to adjuvant radio/chemotherapy two subgroups of patients were analyzed in parallel: patients subjected only to surgery (26 persons) and patients treated with adjuvant therapy (39 persons). As expected, in neither subgroup significant differences between samples A and B were found. Surprisingly, also when samples A and C were compared differences for none of spectral components reached the level of statistical significance (q < 0.1) in both groups of patients, which apparently was related to smaller numbers of samples in these subgroups. However, clear differences were observed between two groups of patients when samples B and C were compared. Several spectral components changed their abundance significantly between these two time points when samples from patients subjected to adjuvant therapy were analyzed. The q-value of the difference in abundance of 26 spectral components reached the level of <0.1 when serum samples from this subgroup were analyzed (Figure 2A). In marked contrast, none of spectral components changed their abundance significantly between time points B and C when samples of patients subjected only to surgery were analyzed (Figure 2B). Noteworthy, 16 out of 26 spectral components that differentiated samples B and C in the subgroup subjected to adjuvant therapy also differentiated samples B and C when the group of whole patients were analyzed (at the level of q-value < 0.1; Table 1). We conclude that differences in serum proteome patterns observed between samples collected after the surgery and one year after the end of basic therapy were specific for the group of patients subjected to adjuvant therapy, and this reflects changes related to this treatment.

Bottom Line: On the other hand, significant long-term effects were observed in serum proteome patterns one year after the end of basic treatment (we found that about 20 peptides exhibited significant changes in their abundances).Moreover, the significant differences were found primarily in the subgroup of patients treated with adjuvant therapy, but not in the subgroup subjected only to surgery.On the other hand, no significant correlation was found between changes in the abundance of any spectral component or clinical features of patients, including staging and grading of tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.

ABSTRACT

Background: The proteomics approach termed proteome pattern analysis has been shown previously to have potential in the detection and classification of breast cancer. Here we aimed to identify changes in serum proteome patterns related to therapy of breast cancer patients.

Methods: Blood samples were collected before the start of therapy, after the surgical resection of tumors and one year after the end of therapy in a group of 70 patients diagnosed at early stages of the disease. Patients were treated with surgery either independently (26) or in combination with neoadjuvant chemotherapy (5) or adjuvant radio/chemotherapy (39). The low-molecular-weight fraction of serum proteome was examined using MALDI-ToF mass spectrometry, and then changes in intensities of peptide ions registered in a mass range between 2,000 and 14,000 Da were identified and correlated with clinical data.

Results: We found that surgical resection of tumors did not have an immediate effect on the mass profiles of the serum proteome. On the other hand, significant long-term effects were observed in serum proteome patterns one year after the end of basic treatment (we found that about 20 peptides exhibited significant changes in their abundances). Moreover, the significant differences were found primarily in the subgroup of patients treated with adjuvant therapy, but not in the subgroup subjected only to surgery. This suggests that the observed changes reflect overall responses of the patients to the toxic effects of adjuvant radio/chemotherapy. In line with this hypothesis we detected two serum peptides (registered m/z values 2,184 and 5,403 Da) whose changes correlated significantly with the type of treatment employed (their abundances decreased after adjuvant therapy, but increased in patients treated only with surgery). On the other hand, no significant correlation was found between changes in the abundance of any spectral component or clinical features of patients, including staging and grading of tumors.

Conclusions: The study establishes a high potential of MALDI-ToF-based analyses for the detection of dynamic changes in the serum proteome related to therapy of breast cancer patients, which revealed the potential applicability of serum proteome patterns analyses in monitoring the toxicity of therapy.

Show MeSH
Related in: MedlinePlus