Proteomic Profiling and Interactome Analysis of ER-Positive/HER2/neuNegative Invasive Ductal Carcinoma of the Breast: Towards Proteomics Biomarkers

Abstract

Breast cancer, especially ER positive/HER2/neu negative IDC, is the predominant subtype of invasive ductal carcinoma. Although proteomic approaches have been used towards biomarker discovery in clinical breast cancer, ER positive/HER2/neu negative IDC is the least studied subtype. To discover biomarkers, as well as to understand the molecular events associated with disease progression of estrogen receptor positive/HER2/neu negative subtype of invasive ductal carcinoma, differential protein expression profiling was performed by using LC-MS(E) (MS at elevated energy). A total of 118 proteins were identified, of which 26 were differentially expressed. These identified proteins were functionally classified and their interactions and coexpression were analyzed by using bioinformatic tools PANTHER (Protein Analysis THrough Evolutionary Relationships) and STRING (Search Tool for the Retrieval of Interacting Genes). These proteins were found to be upregulated and were involved in cytoskeletal organization, calcium binding, and stress response. Interactions of annexin A5, actin, S100 A10, glyceraldehyde 3 phosphate dehydrogenase, superoxide dismutase 1, apolipoprotein, fibrinogen, and heat shock proteins were prominent. Differential expression of these proteins was validated by two-dimensional gel electrophoresis and Western blot analysis. The cluster of these proteins may serve as a signature profile for estrogen receptor positive/ HER2/neu negative subtype.

Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics

“…Another problem with mammography is that it fails to detect the tumor in young women as dense breast tissue has a tendency to decrease mammographic sensitivity . Various quantitative proteomic‐based studies have been pursued to identify potential biomarkers for breast cancer in a variety of clinical samples such as the nipple aspirate fluids , serum , saliva , and tissue . The number of proteomics‐based studies related to breast cancer is increasing exponentially.…”

Profilin-1 Overexpression in MDA-MB-231 Breast Cancer Cells Is Associated with Alterations in Proteomics Biomarkers of Cell Proliferation, Survival, and Motility as Revealed by Global Proteomics Analyses

“…Mortality of breast cancer patients results primarily from distant metastasis of tumor cells to the vital organs. Global analyses or systems science approaches with omics technologies offer concrete ways forward in biomarker discovery for breast cancer (Korwar et al, 2013). Deregulation of the actin cytoskeleton is a hallmark of both oncogenic transformation and deregulated motility of cancer cells leading to metastatic dissemination.…”

Cancer associated proteins in blood plasma: Determining normal variation

“…In addition, we added transitions for additional peptides for the 182 proteins based on Malmström et al, Korwar et al and Dzieciatkowska et al [28][29][30]. In order to maximize the possibility of detection for each protein in our samples, we also updated the peptides for five of our proteins in our transition list based on [30], and included five additional proteins from [26,27,[29][30][31], making the total number of initial CAPs in our study 187 (Supporting Information Table 1). As the number of transitions exceeded the capacity of one scheduled SRM method, we evaluated all transitions in pooled depleted plasma to determine which transitions were detectable in our samples.…”