학술논문
Identification of BRCA1/2 mutation female carriers using circulating microRNA profiles
Document Type
article
Author
Kevin Elias; Urszula Smyczynska; Konrad Stawiski; Zuzanna Nowicka; James Webber; Jakub Kaplan; Charles Landen; Jan Lubinski; Asima Mukhopadhyay; Dona Chakraborty; Denise C. Connolly; Heather Symecko; Susan M. Domchek; Judy E. Garber; Panagiotis Konstantinopoulos; Wojciech Fendler; Dipanjan Chowdhury
Source
Nature Communications, Vol 14, Iss 1, Pp 1-9 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
Abstract Identifying germline BRCA1/2 mutation carriers is vital for reducing their risk of breast and ovarian cancer. To derive a serum miRNA-based diagnostic test we used samples from 653 healthy women from six international cohorts, including 350 (53.6%) with BRCA1/2 mutations and 303 (46.4%) BRCA1/2 wild-type. All individuals were cancer-free before and at least 12 months after sampling. RNA-sequencing followed by differential expression analysis identified 19 miRNAs significantly associated with BRCA mutations, 10 of which were ultimately used for classification: hsa-miR-20b-5p, hsa-miR-19b-3p, hsa-let-7b-5p, hsa-miR-320b, hsa-miR-139-3p, hsa-miR-30d-5p, hsa-miR-17-5p, hsa-miR-182-5p, hsa-miR-421, hsa-miR-375-3p. The final logistic regression model achieved area under the receiver operating characteristic curve 0.89 (95% CI: 0.87–0.93), 93.88% sensitivity and 80.72% specificity in an independent validation cohort. Mutated gene, menopausal status or having preemptive oophorectomy did not affect classification performance. Circulating microRNAs may be used to identify BRCA1/2 mutations in patients of high risk of cancer, offering an opportunity to reduce screening costs.