Abstract 5691: Identification of miRNA related to triple-negative breast cancer in African and European American women with obesity
Authors: Hossain Fokhrul , González-Ramírez Martha Isabel , Garai Jone , Wu Xiao-Cheng , Hicks Chindo , Valle Luis Del , Ochoa Augusto , Danos Denise , Miele Lucio , Zabaleta Jovanny 
Published: March 2024

Triple-negative breast cancer (TNBC) represents 10-20% of all invasive breast cancers and is characterized by a lack of expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC typically manifests as high-grade tumors often diagnosed at advanced stages, and affects younger patients, especially African American (AA) women. Dysregulation of miRNA expression levels contributes to TNBC pathogenesis and prognosis. Dysregulated miRNAs in advanced-stage cancers alter tumor progression, migration, and metastasis. Obesity is associated with miRNA dysregulation in adipose tissue, which is a driver of BC development and growth. This study aimed at identifying differentially expressed (DE) miRNA in TNBC patients of European American (EA) and AA women with obesity, compared to adjacent non-tumor tissues. miRNAseq data from 48 tissue samples (TNBC tumor and adjacent non-tumor) were analyzed for differential expression. Samples were from 12 EA and 12 AA patients, with 6 patients in each ethnic group having obesity and 6 normal weight, based on BMI estimates. Stringent comparisons, with and without obesity, were conducted to identify TNBC and obesity-associated miRNAs within each ethnic group. Prediction of miRNA-target genes was performed in miRWalk and Key Pathway Advisor (KPA) was employed for pathway enrichment analysis. Differential expression analysis between obese and normal-weight patients in each ethnic group revealed 79 DE miRNAs in EA and 40 in AA. We identified 55 miRNAs associated exclusively with tumors in obese patients within the EA group and 33 miRNAs within the AA group. Target gene analysis showed that in EA, 9 out of the 55 miRNAs interacted with 68 mRNAs, with miR-204-5p and miR-181b-5p accounting for 75% of interactions. In AA, 20 out of the 33 miRNAs interacted with 284 mRNAs with miR-20a-5p, -195-5p, -34a-5p, and -130a-3p with 65% of the interactions. KPA identified 84 and 330 pathways for EA and AA, respectively, with 43 common pathways,15 of them related to cancer processes sharing the gene targets GSKIP, TLBR1, TCF4, and TCF. Our study outlined unique miRNA profiles in TNBC among AA and EA women with obesity. Although common mRNAs were identified between ethnic groups, leading to the identification of common pathways on KPA, more than 50% of the identified pathways are related to unique biological processes associated with TNBC and obesity for each ethnic group. These findings underscore the importance of considering ethnic-specific miRNA signatures for understanding TNBC in the context of obesity, offering insights for targeted therapeutic strategies.

Citation Format: Fokhrul Hossain, Martha Isabel González-Ramírez, Jone Garai, Xiao-Cheng Wu, Chindo Hicks, Luis Del Valle, Augusto Ochoa, Denise Danos, Lucio Miele, Jovanny Zabaleta. Identification of miRNA related to triple-negative breast cancer in African and European American women with obesity [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 5691.