Namita Pendharkar1,2, Snigdha Dhali2, Subodhini Abhang1. 1. Biochemistry Department, B.J. Medical College, Sassoon Hospital, Pune, 411001 MH, India. 2. Proteomics Lab, National Centre for Cell Science, Pune, 411007 MH, India.
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.
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.
Authors: Abdullah Saleh Al-Wajeeh; Salizawati Muhamad Salhimi; Majed Ahmed Al-Mansoub; Imran Abdul Khalid; Thomas Michael Harvey; Aishah Latiff; Mohd Nazri Ismail Journal: PLoS One Date: 2020-01-16 Impact factor: 3.240