Comparative microRNA profiling of sporadic and BRCA1 associated basal-like breast cancers

Yan, Max, Shield-Artin, Kristy, Byrne, David, Deb, Siddhartha, Waddell, Nic, kConFab Investigators, kConFab, Haviv, Izhak and Fox, Stephen B. (2015) Comparative microRNA profiling of sporadic and BRCA1 associated basal-like breast cancers. BMC Cancer, 15 1: 1-13. doi:10.1186/s12885-015-1522-4

Author Yan, Max
Shield-Artin, Kristy
Byrne, David
Deb, Siddhartha
Waddell, Nic
kConFab Investigators
Haviv, Izhak
Fox, Stephen B.
Title Comparative microRNA profiling of sporadic and BRCA1 associated basal-like breast cancers
Journal name BMC Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2015-07-08
Sub-type Article (original research)
DOI 10.1186/s12885-015-1522-4
Open Access Status DOI
Volume 15
Issue 1
Start page 1
End page 13
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2016
Language eng
Formatted abstract
Background:  While a number of studies have examined miRNA profiles across the molecular subtypes of breast cancer, it is unclear whether BRCA1 basal-like cancers have a specific miRNA profile. This study aims to compare grade independent miRNA expression in luminal cancers, sporadic and BRCA1 basal-type breast cancers. It also aims to ascertain an immunohistochemical profile regulated by BRCA1 specific miRNAs for potential diagnostic use.

Methods:  miRNA expression was assessed in 11 BRCA1 basal, 16 sporadic basal, 17 luminal grade 3 cancers via microarrays. The expression of Cyclin D1, FOXP1, FIH-1, pan-ERβ, NRP1 and CD99, predicted to be regulated by BRCA1 specific miRNAs by computer prediction algorithms, was assessed via immunohistochemistry in a cohort of 35 BRCA1 and 52 sporadic basal-like cancers. Assessment of cyclin D1, FOXP1, NRP1 and CD99 expression was repeated on a validation cohort of 82 BRCA1 and 65 sporadic basal-like breast cancers.

Results:  Unsupervised clustering of basal cancers resulted in a “sporadic” cluster of 11 cancers, and a “BRCA1” cluster of 16 cancers, including a subgroup composed entirely of 10 BRCA1 cancers. Compared with sporadic basal cancers, BRCA1 cancers showed reduced positivity for proteins predicted to be regulated by miRNAs: FOXP1 (6/20[30 %] vs. 37/49[76 %], p < 0.001), cyclin D1 (8/22[36 %] vs. 30/46[65 %], p = 0.025), NRP1 (2/20[10 %] vs. 23/46[50 %], p = 0.002). This was confirmed in the validation cohort (all p < 0.001). Negative staining for 2 or more out of FOXP1, cyclin D1 and NRP1 predicts germline BRCA1 mutation with a sensitivity of 92 %, specificity of 44 %, positive predictive value of 38 % and a negative predictive value of 94 %.

Conclusion:  Sporadic and BRCA1 basal-like cancers have grade independent miRNA expression profiles. Furthermore miRNA driven differences in the expression of proteins in BRCA1 basal cancers may be detected via immunohistochemistry. These findings may have important diagnostic implications, as immunohistochemical assessment of basal cancers, in addition to the patient’s family and clinical history, may potentially identify patients who may benefit from BRCA1 gene testing.
Keyword Basal-like
Breast cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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