Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy

Abstract

A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; Po0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

“…In support of this, using serum protein profiling, several groups have recently reported increased serum levels of other apolipoproteins in patients with several types of cancer (Yu et al, 2005;Goncalves et al, 2006). On the other hand, Ehmann et al (2007) recently found that serum levels of different apolipoproteins (ApoA-1 and -2) were decreased in pancreatic cancer patients compared with healthy volunteers.…”

Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes

“…SELDI-based protein profiling in oncology was recently investigated as a promising way to identify potential early diagnosis-related biomarkers using biological fluids, such as serum, plasma, or urine, as surrogate tissues inside which tumor fingerprints could be detected. Although various studies have suggested exciting perspectives in the diagnostic (12,13,42) or theragnostic fields (14), most of the proteins actually identified were highly abundant, nonspecific, host response-generated proteins. To get access to tumor-specific biomarkers, global MS-based protein profiling strategies were recently applied to solid tumor samples directly on frozen tissues including brain and lung tumors (43)(44)(45) and have shown promising ability to separate between clinically or pathologically relevant groups of tumor.…”

Plasma and tissue proteomic prognostic factors of response in primary breast cancer patients receiving neoadjuvant chemotherapy

“…The use of such a technique in relation to therapeutic response prediction has been limited (20). In the present study, we used this technology on both plasma and cytosols to predict the therapeutic response in a series of breast cancer patients receiving neoadjuvant chemotherapy.…”