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

Abstract

BackgroundThe 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.MethodsBlood 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.ResultsWe 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.ConclusionsThe 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.

Serum Proteome Signature of Radiation Response: Upregulation of Inflammation-Related Factors and Downregulation of Apolipoproteins and Coagulation Factors in Cancer Patients Treated With Radiation Therapy—A Pilot Study

“…This finding agreed with results of previous studies, where changes induced in serum peptidome by adjuvant radiation and chemotherapy treatment for breast cancer (6) or IMRT for HNSCC (12) could be detected in the blood of patients even 1 year after the end of treatment. Similarly, radiation-related changes could be detected in blood proteome of atom-bomb survivors and victims of radiation accidents several years after exposure (13,18).…”

“…Several components of these signatures, especially those characteristic of advanced cancer, were identified as proteins (or their fragments) involved in systemic response of the patient's body to the disease (eg, inflammation). Furthermore, profiling of serum plasma proteome of patients undergoing anticancer therapy revealed features apparently associated with general toxicity of the treatment to the patient's organism (4)(5)(6). There are several reports documenting effects of ionizing radiation (eg, partial body irradiation received during cancer patients' radiation therapy [RT]).…”

VeriStrat® has a prognostic value for patients with advanced non-small cell lung cancer treated with erlotinib and bevacizumab in the first line: Pooled analysis of SAKK19/05 and NTR528

“…Although we cannot explain the discrepancy between our data and the previous study, it is possible that VS may perform differently in untreated and in chemotherapy-pretreated patients. Cancer-drugs modulate tumors and micro-environment, which has implications for serum proteomic patterns, as demonstrated, for example, in breast cancer patients [14,15]. Alternative explanations may be related to some inherent, but unaccounted for, differences between patients and trials, or to the relatively small number of patients in previously studied cohorts.…”

Identification of Potential Markers Related to Neoadjuvant Chemotherapy Sensitivity of Breast Cancer by SELDI-TOF MS

“…[23] Moreover, there were similar peaks between our results and what reported previously on serum samples (approximate registered m/z values 2,742, 3,992, 5,877, 6,489,8,888,8,931,8,942, and 8,973 Da). [24] Notably, protein peak at 8.9 kDa has been reported in numerous previous studies, [17,18,[20][21][22][23][24][25] indicating its potential values in the diagnosis of breast cancer and the evaluation of treatments and NACT.…”