Validation of previously identified serum biomarkers for breast cancer with SELDI-TOF MS: a case control study

Abstract

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.

Clinical proteomics in breast cancer: a review

“…Subsequent analysis of an independent sample set could only confirm the increased 8.1 and 8.9 kDa C3a fragments [42]. However, the 8.1 kDa C3a desArgD8 was found to lack significance in a second [43] and third validation study [44]. The latter study also reported a decreased 8.9 kDa C3a desArg expression in breast cancer [44], whereas in all previous studies, this fragment was found increased [41][42][43].…”

“…However, the 8.1 kDa C3a desArgD8 was found to lack significance in a second [43] and third validation study [44]. The latter study also reported a decreased 8.9 kDa C3a desArg expression in breast cancer [44], whereas in all previous studies, this fragment was found increased [41][42][43]. Beyond these four studies, C3a desArg has been found associated with survival, as its expression decreased in metastatic relapse [45].…”

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

“…In proteomic profiling studies in gastric cancer of comparable sample size and design performed by others, changes could not be identified. Several studies analyzing disease-specific proteomic patterns, in search of novel diagnostic or predictive biomarkers in advanced and early breast cancer patients have been published (23,24). 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.…”

Modern approach of breast cancer diagnostics

“…(табл. 2) [35][36][37][38][39][40][41][42][43][44][45][46].Интересно отметить, что большинство идентифицированных белков не является продуктом опухолевых клеток, а относится к неспецифическим белкам воспаления. Вопрос о том, насколько могут быть применимы такие белки для онкодиагностики, является предметом острой дискуссии.…”