Breast cancer identification via modeling of peripherally circulating miRNAs

Abstract

Prolonged life expectancy in humans has been accompanied by an increase in the prevalence of cancers. Breast cancer (BC) is the leading cause of cancer-related deaths. It accounts for one-fourth of all diagnosed cancers and affects one in eight females worldwide. Given the high BC prevalence, there is a practical need for demographic screening of the disease. In the present study, we re-analyzed a large microRNA (miRNA) expression dataset (GSE73002), with the goal of optimizing miRNA biomarker selection using neural network cascade (NNC) modeling. Our results identified numerous candidate miRNA biomarkers that are technically suitable for BC detection. We combined three miRNAs (miR-1246, miR-6756-5p, and miR-8073) into a single panel to generate an NNC model, which successfully detected BC with 97.1% accuracy in an independent validation cohort comprising 429 BC patients and 895 healthy controls. In contrast, at least seven miRNAs were merged in a multiple linear regression model to obtain equivalent diagnostic performance (96.4% accuracy in the independent validation set). Our findings suggested that suitable modeling can effectively reduce the number of miRNAs required in a biomarker panel without compromising prediction accuracy, thereby increasing the technical possibility of early detection of BC.

Keywords

• microRNA
• Breast cancer
• Diagnostic biomarker
• Neural network cascade