Clinical proteomics in breast cancer: a review

Abstract

Breast cancer imposes a significant healthcare burden on women worldwide. Early detection is of paramount importance in reducing mortality, yet the diagnosis of breast cancer is hampered by the lack of an adequate detection method. In addition, better breast cancer prognostication may improve selection of patients eligible for adjuvant therapy. Hence, new markers for early diagnosis, accurate prognosis and prediction of response to treatment are warranted to improve breast cancer care. Since proteomics can bridge the gap between the genetic alterations underlying cancer and cellular physiology, much is expected from proteome analyses for the detection of better protein biomarkers. Recent technical advances in mass spectrometry, such as matrix-assisted laser desorption/ ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and its variant surface-enhanced laser desorption/ ionisation (SELDI-) TOF MS, have enabled highthroughput proteome analysis. In the current review, we give a comprehensive overview of the results of expression proteomics (i.e. protein profiling) research performed in breast cancer using these two platforms. Many protein peaks have been reported to bear significant diagnostic, prognostic or predictive value, however, only few candidate markers have been structurally identified yet. In addition, although of pivotal importance in preventing overfitting of data and systematic bias by pre-analytical parameters, validation of biomarker candidates by other, quantitative, methods and/or in new populations is very limited. Moreover, none of the identified candidate biomarkers has been investigated for their utility as breast cancer markers in large, prospective, clinical settings. As such, the candidate biomarkers discussed in this overview have not been validated sufficiently to be used for clinical patient care. Nonetheless, regarding the promising results up to now, MALDI-and SELDI-TOF MS protein profiling studies could eventually fulfil the great promise that protein biomarkers have for improving cancer patient outcome, provided that these studies are performed with adequate statistical power and analytical rigour.

Fluopsin C induces oncosis of human breast adenocarcinoma cells

“…As shown in Figure 2, cells treated with fluopsin C (0.5 to 8 μmol/L) for different times (6,12, and 24 h) exhibited a decrease in viability in a dose-and time-dependent manner. The IC 50 values were 2.9, 1.6, and 0.9 μmol/L for MCF-7 cells and 2. μmol/L at 6, 12, and 24 h, respectively), suggesting the necessity of investigating the anticancer activity of fluopsin C and considering its toxicity in future clinical use and drug development.…”

Serum proteomics and disease-specific biomarkers of patients with advanced gastric cancer

“…Irrespective of the different clinical setting and technical approach, most of these analyses found an association between several known proteins or their fragments, such as diverse apolipoproteins, complement factors, fibrinogen and haptoglobin. Many of these have been shown not to be disease-specific, and none have been validated in a prospective clinical study (25). the most differentiating proteins, based on their relative importance of the peak value in the classification between gastric cancer patients and matched normal control subjects (table IV), varied on different days of analysis.…”

Proteomic studies in breast cancer (Review)

“…(70) demonstrated that cell lines of human cancer which increased expression of 14-3-3σ contributed to drug resistance, suggesting that such a change is associated with clinical resistance to chemotherapy. In treatments stimulating apoptosis, ubiquitin and S100-A6 decreased in the lysates of breast cancer cell lines, and aberrant expression of the two proteins in breast cancer tissue was found (71). In recent studies, a proteomic analysis of 14 matched pairs of tumor tissues (ER-positive) prior to and following neoadjuvant treatment with aromatase inhibitor (AI) revealed 10 differentially expressed proteins.…”