Abstract
Breast cancer is the most common malignancy among women globally. Development of a reliable plasma biomarker panel might serve as a non-invasive and cost-effective means for population-based screening of the disease. Transcriptomic profiling of breast tumour, paired normal and apparently normal tissues, followed by validation of the shortlisted genes using TaqMan® Low density arrays and Quantitative real-time PCR was performed in South Asian women. Fifteen candidate protein markers and 3 candidate epigenetic markers were validated first in primary breast tumours and then in plasma samples of cases [N = 202 invasive, 16 DCIS] and controls [N = 203 healthy, 37 benign] using antibody array and methylation specific PCR. Diagnostic efficiency of single and combined markers was assessed. Combination of 6 protein markers (Adipsin, Leptin, Syndecan-1, Basic fibroblast growth factor, Interleukin 17B and Dickopff-3) resulted in 65% sensitivity and 80% specificity in detecting breast cancer. Multivariate diagnostic analysis of methylation status of SOSTDC1, DACT2, WIF1 showed 100% sensitivity and up to 91% specificity in discriminating BC from benign and controls. Hence, combination of SOSTDC1, DACT2 and WIF1 was effective in differentiating breast cancer [non-invasive and invasive] from benign diseases of the breast and healthy individuals and could help as a complementary diagnostic tool for breast cancer.
Highlights
Breast cancer is the most common malignancy among women globally
Carcinoembryonic antigen (CEA)[8,9], human epidermal growth factor receptor-2 (HER2)[10,11], the oncogenic protein RS/DJ-112, tissue polypeptide antigen (TPA)[13] tissue polypeptide specific antigen (TPS)[14] and CA 15–315,16 have been recommended as biomarkers for metastatic Breast Cancer (BC), as they were deficient in early BC detection
A transcriptomic profile using microarray was obtained from 41 primary breast tumours (T), 18 paired normal (PN) and 6 apparent normal (AN) tissues procured from South Asian women
Summary
Breast cancer is the most common malignancy among women globally. Development of a reliable plasma biomarker panel might serve as a non-invasive and cost-effective means for population-based screening of the disease. The protein marker panel lacked the desired diagnostic power, 3 candidate genes which were found to be downregulated in our BC microarray study and confirmed to be methylated in tumours but not in normal breast tissue or in peripheral blood mononuclear cells (PBMC) were chosen for epigenetic marker evaluation. Detection of these methylated genes in cfDNA was performed in the same set of subjects recruited for the protein marker study. The circulating methylation biomarkers achieved 100% sensitivity and up to 90% specificity in discrimination of BC from benign cases and controls
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