A Novel Strategy to Investigate Tissue‐Secreted Tumor Microenvironmental Proteins in Serum toward Development of Breast Cancer Early Diagnosis Biomarker Signature

Abstract

Purpose: The study aims to discover and identify early grade diagnosis markers in tumor microenvironment and investigates their expression in serum. Experimental design: 2D fluorescence difference gel electrophoresis (2D-DIGE), a gel-based proteomics platform is used for tissue profiling and identifies deregulated proteins by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Western blot validation for statistically significant six different proteins is performed in an independent cohort of participant serum. Results: Total 67 nonredundant tissue proteins are identified out of 230 protein spots obtained through Marker selection tool of EDA. GELS, DAPLE, IQCC, CATD, A1AT, and HS90B are selected for validation and found to be upregulated in early grade serum samples. Pathway analysis performed through PANTHER and DAVID indicates that apoptosis, CCKR, EGF, FAS, FGF, Wnt, p13 kinase, and p53 signaling pathways are expressed specifically during or early onset of grade I cancer lesions. Conclusions and clinical relevance: GELS, DAPLE, HS90B, A1AT, IQCC, and CATD may be promising potential serum biomarker signature for diagnosis of early grade breast cancer. This panel also contributes to better understanding of molecular mechanisms involved in inceptive stage of breast cancer.

Five microRNAs in Serum Are Able to Differentiate Breast Cancer Patients From Healthy Individuals

“…On the other hand, differently expressed proteins in the serum of breast cancer patients vs. controls have been described (39). The deregulated proteins found in the pools of cancer vs. control serum samples-PEDF, IGKC, CD44, and CST3-have been previously reported (39)(40)(41).…”

“…On the other hand, differently expressed proteins in the serum of breast cancer patients vs. controls have been described (39). The deregulated proteins found in the pools of cancer vs. control serum samples-PEDF, IGKC, CD44, and CST3-have been previously reported (39)(40)(41). High levels of CD44 in serum are an independent prognosis indicator in primary breast cancer, since it correlates with overall survival and disease-free survival (42).…”

Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome

“…One of these is HS90B, which was also present in EXOs isolated from five GBM cell lines [110], and shows a potential functional network with other important molecules with co-chaperone activities (see Figure 3 and Table S4). Indeed, HS90B has a role in cancer progression, together with proteins including GRP75 and VIME (reported in our Table 1), and as a potential biomarker, useful for diagnostic and therapeutic applications in malignant melanoma cancer [111] or early grade breast cancer [112]. Furthermore, it has been related to tumors' chemo-and radio-resistance, also showing angiogenic properties [101].…”

Comparative proteomic analysis of different stages of breast cancer tissues using ultra high performance liquid chromatography tandem mass spectrometer

“…Gelsolin, Protein Daple, Heat shock protein HSP 90-beta, Alpha-1-antitrypsin, and Cathepsin D constitute serum biomarker signature for diagnosing early grade breast cancer. The panel of proteins also provides crucial information for a better understanding of molecular mechanisms underlying the inceptive stage of breast cancer [104]. Recently, Gomig et al [105] showed a high similarity in the proteomic profile between contralateral and adjacent nontumor breast tissues.…”