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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 the abundance of spectral components that correlates with the type of therapy. Shown are intensities of two spectral components, m/z = 2184 and 5403, in serum samples collected after surgery (sample B) and one year after the end of basic therapy (sample C). Each component either increased (I) or decreased (D) between samples B and C (upper left and bottom right halves of the graph, respectively); the red dots represent patients subjected to surgery and adjuvant therapy, green boxes represent patients subjected only to surgery.
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Figure 4: Changes in the abundance of spectral components that correlates with the type of therapy. Shown are intensities of two spectral components, m/z = 2184 and 5403, in serum samples collected after surgery (sample B) and one year after the end of basic therapy (sample C). Each component either increased (I) or decreased (D) between samples B and C (upper left and bottom right halves of the graph, respectively); the red dots represent patients subjected to surgery and adjuvant therapy, green boxes represent patients subjected only to surgery.

Mentions: In the next step we analyzed whether changes in abundance of a given spectral component registered in samples collected after surgery and one year after the end of basic therapy correlated with clinical data; two clusters of samples were separated where the component's intensity either increased or decreased between points B and C. We found that modality in changes of two spectral components (m/z = 5403 and 2184 Da) correlated significantly with the scheme of therapy (p-value 0.00003 and 0.00005, respectively). Figure 4 shows that the abundance of both components most likely decreased in serum of patients treated with the adjuvant therapy while these increased in serum of patients subjected only to surgery. In addition, we analyzed the possible associations between modality in changes of each spectral component and each of 20 available "classical" clinical features, which among others included: age, different measures of staging and grading, estrogen and progesterone receptor expression, HER2 status, leukocyte and hemoglobin levels. Importantly, a correlation between any of these clinical features and changes in intensity of any spectral component did not remain statistically significant when a Bonferroni correction for multiple testing was applied. Noteworthy, however, among ~200 pairs of features (i.e., spectral component vs. clinical feature; 8000 pairs were possible overall) that showed some tendency to associate (i.e. uncorrected p-value < 0.05), there were 43 spectral components that correlated with expression of either the progesterone or estrogen receptor. This tendency suggests that certain changes observed between samples collected after surgery and one year after the end of basic therapy were related to anti-estrogen treatment ongoing in patients with a high level of expression of estrogen/progesterone receptors.


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 the abundance of spectral components that correlates with the type of therapy. Shown are intensities of two spectral components, m/z = 2184 and 5403, in serum samples collected after surgery (sample B) and one year after the end of basic therapy (sample C). Each component either increased (I) or decreased (D) between samples B and C (upper left and bottom right halves of the graph, respectively); the red dots represent patients subjected to surgery and adjuvant therapy, green boxes represent patients subjected only to surgery.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Changes in the abundance of spectral components that correlates with the type of therapy. Shown are intensities of two spectral components, m/z = 2184 and 5403, in serum samples collected after surgery (sample B) and one year after the end of basic therapy (sample C). Each component either increased (I) or decreased (D) between samples B and C (upper left and bottom right halves of the graph, respectively); the red dots represent patients subjected to surgery and adjuvant therapy, green boxes represent patients subjected only to surgery.
Mentions: In the next step we analyzed whether changes in abundance of a given spectral component registered in samples collected after surgery and one year after the end of basic therapy correlated with clinical data; two clusters of samples were separated where the component's intensity either increased or decreased between points B and C. We found that modality in changes of two spectral components (m/z = 5403 and 2184 Da) correlated significantly with the scheme of therapy (p-value 0.00003 and 0.00005, respectively). Figure 4 shows that the abundance of both components most likely decreased in serum of patients treated with the adjuvant therapy while these increased in serum of patients subjected only to surgery. In addition, we analyzed the possible associations between modality in changes of each spectral component and each of 20 available "classical" clinical features, which among others included: age, different measures of staging and grading, estrogen and progesterone receptor expression, HER2 status, leukocyte and hemoglobin levels. Importantly, a correlation between any of these clinical features and changes in intensity of any spectral component did not remain statistically significant when a Bonferroni correction for multiple testing was applied. Noteworthy, however, among ~200 pairs of features (i.e., spectral component vs. clinical feature; 8000 pairs were possible overall) that showed some tendency to associate (i.e. uncorrected p-value < 0.05), there were 43 spectral components that correlated with expression of either the progesterone or estrogen receptor. This tendency suggests that certain changes observed between samples collected after surgery and one year after the end of basic therapy were related to anti-estrogen treatment ongoing in patients with a high level of expression of estrogen/progesterone receptors.

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