Therapy-Related Changes in the Serum Proteome Patterns of Early Stage Breast Cancer Patients with Different Outcomes
2016
Adjuvant chemo- and/or radiotherapy is applied in a majority of patients treated for early
stage breast cancer, although only a small percentage of these individuals are at high risk of metastasis
or recurrence. Hence, knowledge of the biomarkers associated with the risk of disease progression
might facilitate the planning of an optimal therapy and protect many patients from the toxicity of
unnecessary treatment. In this study, we characterized the serum proteome of patients diagnosed with
early-stage breast cancer, exhibiting either no evidence of disease five years after the end of therapy
or suffering from metastasis, relapse or a second cancer during the corresponding follow-up. Samples
collected before treatment and one year after the end of therapy, when no clinical symptoms of a
treatment failure was evidenced, were analyzed using two classical proteomics approaches:
LC-MS/MS and 2D-PAGE. A total of 42 proteins with relative quantities that were significantly
different between pre- and post-treatment samples were identified in either group of patients; however,
the observed changes were more frequent in the treatment-failure group. Among the posttreatment
samples, 30 proteins were upregulated, and 10 proteins were downregulated, while 11 proteins
were upregulated, and eight proteins were downregulated in the control group. Moreover, several
proteins exhibited different patterns of changes in both groups of patients. For example, haptoglobin
expression increased in the treatment-failure group but decreased in the control group (this
pattern of changes was confirmed using an immunoassay). Notably, proteins affected in posttreatment
samples in either group of patients could be associated with different molecular and cellular
functions, including angiogenesis, blood coagulation and wound healing in the treatment-failure
group and cell adhesion and cell death in the control group.
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