Identification and validation of plasma biomarkers for diagnosis of breast cancer in South Asian women

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((R)) 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.

Automated summary

Breast cancer is the most common malignancy in women globally. The development of a reliable plasma biomarker panel could provide a non-invasive and cost-effective method for population-based screening of the disease. This study identified several candidate protein markers and epigenetic markers for breast cancer diagnosis and validated their effectiveness in differentiating breast cancer from benign diseases and healthy individuals. A combination of protein markers demonstrated moderate sensitivity and specificity, while the methylation status of SOSTDC1, DACT2, and WIF1 showed high sensitivity and specificity in distinguishing breast cancer.