Plasma Proteomic Profiling in Hereditary Breast Cancer Reveals a BRCA1-Specific Signature: Diagnostic and Functional Implications

Abstract

BackgroundBreast cancer (BC) is a leading cause of death among women. Among the major risk factors, an important role is played by familial history of BC. Germ-line mutations in BRCA1/2 genes account for most of the hereditary breast and/or ovarian cancers. Gene expression profiling studies have disclosed specific molecular signatures for BRCA1/2-related breast tumors as compared to sporadic cases, which might help diagnosis and clinical follow-up. Even though, a clear hallmark of BRCA1/2-positive BC is still lacking. Many diseases are correlated with quantitative changes of proteins in body fluids. Plasma potentially carries important information whose knowledge could help to improve early disease detection, prognosis, and response to therapeutic treatments. The aim of this study was to develop a comprehensive approach finalized to improve the recovery of specific biomarkers from plasma samples of subjects affected by hereditary BC.MethodsTo perform this analysis, we used samples from patients belonging to highly homogeneous population previously reported. Depletion of high abundant plasma proteins, 2D gel analysis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis were used into an integrated approach to investigate tumor-specific changes in the plasma proteome of BC patients and healthy family members sharing the same BRCA1 gene founder mutation (5083del19), previously reported by our group, with the aim to identify specific signatures.ResultsThe comparative analysis of the experimental results led to the identification of gelsolin as the most promising biomarker.ConclusionsFurther analyses, performed using a panel of breast cancer cell lines, allowed us to further elucidate the signaling network that might modulate the expression of gelsolin in breast cancer.

The Quantitative Levels of Serum Brca1, Total Protein, Albumin, and Serum Protein Electrophoresis Pattern as a Novel Biomarkers of Breast Cancer Correlating in the Familial Breast Cancer Patients in Iraq.

“…[1] Similarly, proteins play a chief role in cell configuration and function. It is a proved fact that serum protein levels may undergo alterations during the course of BC [7] , with many quantitative change levels of protein and protein fractions. [7] The patients in this study were post-mastectomies and the mean serum total protein STP was equal in the both of the two BC groups and significantly higher than that for the HCs.…”

“…It is a proved fact that serum protein levels may undergo alterations during the course of BC [7] , with many quantitative change levels of protein and protein fractions. [7] The patients in this study were post-mastectomies and the mean serum total protein STP was equal in the both of the two BC groups and significantly higher than that for the HCs. The current study disagree with (Jsiem RH, et al 2012) [12] that record decrease serum level in the estimation of serum and / or tissue in bladder cancer.…”

“…[6,7] BRCA1 is a tumor suppressor protein that is potentially useful as TM for screening and identification of high risk individuals and their families.…”

The Quantitative Serum Brca1and Serum Zinc as a Novel Biomarkers With the Correlations Between Them in the Familial Breast Cancer Patients in Iraq.

“…[2,3] and as it well known, BC is not preventable [4] , therefore, earlier detection is the keystone for reduction of mortality5, at this approach, many diseases are correlated with quantitative changes of substances in the fluids, and plasma carries important information which potentially could help to improve early disease detection, prognosis, and response to therapeutic treatments. [6,7] Zinc had been widely reported as an essential trace element and it functions as an antioxidant that play a role in the maintenance of genomic stability [8] , and there was an inverse link between dietary and serum Zn levels with the risk of breast cancer developing.…”

Profiling of Cross-Functional Peptidases Regulated Circulating Peptides in BRCA1 Mutant Breast Cancer

“…15 Finally, a recent study profiled the plasma proteomes of four patients with BRCA1 mutant BC, four healthy carriers, and four healthy relatives and found an association with gelsolin although this was a small study. 14 Better understanding of what drives BRCA1 mutant BC may lead to new biomarkers and new treatments. PARP inhibitors are currently under evaluation as targeted therapy for metastatic BRCA1 mutant BC in a phase III clinical trial; 17 however, there are remaining questions in ongoing targeted therapy research, where better understanding may identify resistance mechanisms and potential therapy targets.…”