MicroRNA expression in pre-treatment plasma of patients with benign breast diseases and breast cancer
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Mirelle Lagendijk1, Sepideh Sadaatmand1, Linetta B. Koppert1, Madeleine M.A. Tilanus-Linthorst1, Vanja de Weerd2, Raquel Ramírez-Moreno2, Marcel Smid2, Anieta M. Sieuwerts2,3 and John W.M. Martens2,3
1Department of Surgical Oncology, Erasmus MC Cancer Institute, EA 3075, Rotterdam, The Netherlands
2Department of Medical Oncology, Erasmus MC Cancer Institute, EA 3075, Rotterdam, The Netherlands
3Cancer Genomics Centre Netherlands, Erasmus University MC, CN 3015, Rotterdam, The Netherlands
Anieta M. Sieuwerts, email: [email protected]
Keywords: microRNA; breast cancer; BRCA1-mutation carriers; micro array; RT-qPCR
Received: October 12, 2017 Accepted: April 06, 2018 Published: May 11, 2018
Background: MicroRNAs (miRs) are small RNA molecules, influencing messenger RNA (mRNA) expression and translation, and are readily detectable in blood. Some have been reported as potential breast cancer biomarkers. This study aimed to identify and validate miRs indicative of breast cancer.
Results: Based on the discovery and literature, 18 potentially informative miRs were quantified in the validation cohort. Irrespective of patient and tumour characteristics, hsa-miR-652-5p was significantly upregulated in the malignant compared to benign patients (1.26 fold, P = 0.005) and therefore validated as potential biomarker. In the validation cohort literature-based hsa-let-7b levels were higher in malignant patients as well (1.53 fold, P = 0.011). Two miRs differentiated benign wildtype from benign BRCA1 mutation carriers and an additional 8 miRs differentiated metastastic (n = 8) from non-metastatic (n = 41) cases in the validation cohort.
Methods: Pre-treatment plasma samples were collected of patients with benign breast disease and breast cancer and divided over a discovery (n = 31) and validation (n = 84) cohort. From the discovery cohort miRs differentially expressed between benign and malignant cases were identified using a 2,000-miR microarray. Literature-based miRs differentiating benign from malignant disease were added. Using RT-qPCR, their expression was investigated in a validation cohort consisting of pre-treatment benign, malignant and metastatic samples. Additionally, benign and malignant cases were compared to benign and malignant cases of BRCA1-mutation carriers.
Conclusions: Plasma microRNA levels differed between patients with and without breast cancer, between benign disease from wildtype and BRCA1-mutation carriers and between breast cancer with and without metastases. Hsa-miR-652-5p was validated as a potential biomarker for breast cancer.
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