Abstract 2987: microRNA (miRNA) a putative biomarker to better define the molecular apocrine breast cancer (MABC) subtype
Authors: Chamandi Ghada , Borgel Adrien , Kurdi Abdallah , Khoueiry Pierre , Teixeira Luis , Bras Morgane Le , Lehamnn Jacqueline , Nasr Rihab 
Published: March 2024

Background: Breast cancer (BC), is a highly heterogeneous disease, divided into molecular subtypes based on gene expression and clinical outcomes. Transcriptomics profiling depicted a subtype that has luminal expression profile but lacks estrogen receptor (ER), progesterone receptor expression with an overlapping expression of HER-2; yet it overexpresses androgen receptor (AR). This subtype was referred to as MABC and constitutes 8-14% of all BC types. At present MABC is often misdiagnosed with triple negative BC (TNBC). Its improper diagnosis demands the adoption of complementary tools; miRNA, key players in BC tumorigenic processes, hold promise in defining MABC.

Methods: 539 BC microarray data were downloaded from The Cancer Genome Atlas (TCGA-BRCA) (PMID: 25691825) using TCGA biolinks R/Bioconductor package (PMID:267704973). Cases with available miRNA data were retained and classified using citbcmst R package (PMID: 21785460). Differential expression analysis identified deregulated miRNAs using DEseq2. The validation set consists of 111 ER-neg samples (68 MABC, and 43 TN samples) with an average age at diagnosis 58.51 years and a median follow-up=78.5 months. MABC tumors were characterized apart of TNBC by the molecular signature (AR, FOXA1 and AR-related genes, PMID: 25516281) on fresh tissue sections. Using miRCURY LNATM miRNA PCR assay, miRNA profiling was done for a panel of differentially expressed miRNAs. Non tumorigenic (MCF-10A) and BC Cellular models MABC (MDA-MB-453) and TNBC (MDA-MB-231) were used to investigate the invasive potential of MABC.

Results: TCGA data analysis indicated MABC as a separate entity based on gene signature. MiRNA-seq data analysis depicted a set of 6 significantly deregulated miRNA with absolute value of log2 fold change&gt; 1 and P-adjusted value &lt;0.05 between MABC and TNBC. We validated, by miRNA profiling, significant upregulation of miR-2115-3p and miR-187-3p in MABC compared to TNBC. These miRNAs significantly differentiate MABC patients from TNBC patients where the combined miRNA panel of miR-2115-3p and miR-187-3p had an area under the curve of 0.904 ±0.28 (P&lt;0.0001 and 95% CI: 0.850-0.958) and sensitivity, specificity, and a diagnostic accuracy of 90.41%, 81.1%, and 86.5% respectively. Preliminary data, showed that non-tumorigenic/non-invasive MCF-10A had a significant increase in its invasive ability upon transfection with miR-187-3p mimic (P&lt;0.05). Similarly, the invasive cell line MDA-MB-231 showed a significant increase in invasion upon transfection with miR-187-3p mimic (P&lt;0.05). On the other hand, only miR-187-3p inhibitor significantly decreased the invasive potential of MDA-MB-453 cells (P&lt;0.05).

Conclusion: MABC has a unique signature of miRNA as compared to TNBC. miR-2115-3p, and miR-187-3p could be potential diagnostic biomarkers for MABC. The invasive potential of MABC could be attributed to miR-187-3p activity.

Citation Format: Ghada Chamandi, Adrien Borgel, Abdallah Kurdi, Pierre Khoueiry, Luis Teixeira, Morgane Le Bras, Jacqueline Lehamnn, Rihab Nasr. microRNA (miRNA) a putative biomarker to better define the molecular apocrine breast cancer (MABC) subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2987.