No 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.

BackgroundSerum protein profiling seems promising for early detection of breast cancer. However, the approach is also criticized, partly because of difficulties in validating discriminatory proteins. This study's aim is to validate three proteins previously reported to be discriminative between breast cancer cases and healthy controls. These proteins had been identified as a fragment of inter-alpha trypsin inhibitor H4 (4.3 kDa), C-terminal-truncated form of C3a des arginine anaphylatoxin (8.1 kDa) and C3a des arginine anaphylatoxin (8.9 kDa).MethodsSerum protein profiles of 48 breast cancer patients and 48 healthy controls were analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Differences in protein intensity between breast cancer cases and controls were measured with the Mann-Whitney U test and adjusted for confounding in a multivariate logistic regression model.ResultsFour peaks, with mass-to-charge ratio (m/z) 4276, 4292, 8129 and 8941, were found that were assumed to represent the previously reported proteins. M/z 4276 and 4292 were statistically significantly decreased in breast cancer cases compared to healthy controls (p < 0.001). M/z 8941 was decreased in breast cancer cases (p < 0.001) and m/z 8129 was not related with breast cancer (p = 0.87). Adjustment for sample preparation day, sample storage duration and age did not substantially alter results.ConclusionM/z 4276 and 4292 both represented the previously reported 4.3 kDa protein and were both decreased in breast cancer patients, which is in accordance with the results of most previous studies. M/z 8129 was in contrast with previous studies not related with breast cancer. Remarkably, m/z 8941 was decreased in breast cancer cases whereas in previous studies it was increased. Differences in patient populations and pre-analytical sample handling could have contributed to discrepancies. Further research is needed before we can conclude on the relevance of these proteins as breast cancer biomarkers.