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

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.