Abstract
miRNAs are noncoding RNAs with abnormal expression in breast cancer; their expression in high-risk benign breast tissue may relate to breast cancer risk. We examined miRNA profiles in contralateral unaffected breasts (CUB) of patients with breast cancer and validated resulting candidates in two additional sample sets. Expression profiles of 754 mature miRNAs were examined using TaqMan Low Density Arrays in 30 breast cancer samples [15 estrogen receptor (ER)-positive and 15 ER-negative] and paired CUBs and 15 reduction mammoplasty controls. Pairwise comparisons identified miRNAs with significantly differential expression. Seven candidate miRNAs were examined using qRT-PCR in a second CUB sample set (40 cases, 20 ER+, 20 ER-) and 20 reduction mammoplasty controls. Further validation was performed in 80 benign breast biopsy (BBB) samples; 40 from cases who subsequently developed breast cancer and 40 from controls who did not. Logistic regression, using tertiles of miRNA expression, was used to discriminate cases from controls. Seven miRNAs were differentially expressed in tumors and CUBs versus reduction mammoplasty samples. Among them, miR-18a and miR-210 were validated in the second CUB set, showing significantly higher expression in tumor and CUBs than in reduction mammoplasty controls. The expression of miR-18a and miR-210 was also significantly higher in BBB cases than in BBB controls. When both miR-18a and miR-210 were expressed in the upper tertiles in BBB, OR for subsequent cancer was 3.20, P = 0.023. miR-18a and miR-210 are expressed at higher levels in CUBs of patients with breast cancer, and in BBB prior to cancer development, and are therefore candidate breast cancer risk biomarkers. Cancer Prev Res; 10(1); 89-97. ©2016 AACR.
Highlights
Breast cancer is a disease driven by progressive genetic abnormalities involving mutations in oncogenes and tumor suppressorNote: Supplementary data for this article are available at Cancer Prevention Research Online.Current address for F.F
The first validation set consisted of tumor, contralateral unaffected breasts (CUB), and reduction mammoplasty samples from 60 subjects that were independent of the discovery set and comparable in terms of age, race, and menopausal status across the 3 groups (Table 1, CUB validation set)
In the benign biopsy validation sample set, 20 estrogen receptor (ER)-positive cases and 20 ER-negative cases were matched on age, race, and menopausal status, which were matched on the same parameters to 40 controls (Table 1, benign breast biopsy (BBB) validation set)
Summary
Breast cancer is a disease driven by progressive genetic abnormalities involving mutations in oncogenes and tumor suppressor. Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/). Current address for F.F. Costa: Genomic Sciences and Biotechnology Program, UCB - Brasilia, SGAN 916 Modulo B, Bloco C, 70.790-160 Brasilia, DF, Brazil; and current address for M.B. Soares: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
