Plasma microRNA ratios associated with breast cancer detection: results from a nested case-control study in an Italian population-based mammography screening cohort

Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. The objective of this study was to identify circulating microRNAs (miRs) ratios associated with BC in women attending mammography screening. A nested case-control study was conducted within the ANDROMEDA cohort (women of age 46-67 attending BC screening in northern Italy), where pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR-ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR-ratios was carried out as a platform validation. Penalized logistic regression was further applied to candidate miR-ratios alone, or in combination with non-molecular factors, to build a diagnostic model. Overall design: Small RNA sequencing for discovery of microRNA ratios associated with BC detection analysed between BC cases and controls obtained in a screening setting. Candidate biomarker miR ratios were then validated using qRT-PCR