A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer

BMC Cancer

Michael C. Campbell¹  Victor Apprey²  Safaa Turkistani³  Yasmine Kanaan³  Ali Afsari⁴  Tammey Naab⁴  Robert L. Copeland⁵  Paolo Fadda⁶  Bruna M. Sugita⁷  Rafael Marchi⁷  Luciane R. Cavalli⁸ 

[1] Department of Biology, Howard University, Washington DC, USA;Department of Community and Family Medicine, Howard University, Washington DC, USA;Department of Microbiology, Howard University Cancer Center, Howard University, Washington DC, USA;Department of Pathology, Howard University Hospital, Washington DC, USA;Department of Pharmacology, College of Medicine and Cancer Center, Howard University, Washington DC, USA;Genomics Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA;Research Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, PR, Brazil;Research Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, PR, Brazil;Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA;

关键词: microRNA;    Triple-negative breast cancer;    African-American;    Prognosis;    Tumor size;    Lymph node;   

DOI  :  10.1186/s12885-021-08573-2

来源: Springer

【 摘 要 】

BackgroundTo investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC).MethodsTwenty-five samples of AA TNBC patients were profiled for global miRNA expression and stratified considering three clinical-pathological parameters: tumor size, lymph node (LN), and recurrence (REC) status. Differential miRNA expression analysis was performed for each parameter, and their discriminatory power was determined by Receiver Operating Characteristic (ROC) curve analysis. KMplotter was assessed to determine the association of the miRNAs with survival, and functional enrichment analysis to determine the main affected pathways and miRNA/mRNA target interactions.ResultsA panel of eight, 23 and 27 miRNAs were associated with tumor size, LN, and REC status, respectively. Combined ROC analysis of two (miR-2117, and miR-378c), seven (let-7f-5p, miR-1255b-5p, miR-1268b, miR-200c-3p, miR-520d, miR-527, and miR-518a-5p), and three (miR-1200, miR-1249-3p, and miR-1271-3p) miRNAs showed a robust discriminatory power based on tumor size (AUC = 0.917), LN (AUC = 0.945) and REC (AUC = 0.981) status, respectively. Enrichment pathway analysis revealed their involvement in proteoglycans and glycan and cancer-associated pathways. Eight miRNAs with deregulated expressions in patients with large tumor size, positive LN metastasis, and recurrence were significantly associated with lower survival rates. Finally, the construction of miRNA/mRNA networks based in experimentally validated mRNA targets, revealed nodes of critical cancer genes, such as AKT1, BCL2, CDKN1A, EZR and PTEN.ConclusionsAltogether, our data indicate that miRNA deregulated expression is a relevant biological factor that can be associated with the poor prognosis in TNBC of AA patients, by conferring to their TNBC cells aggressive phenotypes that are reflected in the clinical characteristics evaluated in this study.

【 授权许可】

CC BY