Abstract
Abstract Introduction: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype, lacking expression of estrogen, progesterone and HER2 receptors. Evidence suggests that TNBC present more frequently in young African-American and Hispanic women, with lower socioeconomic status, hormonal environment and obesity. To this date, there are no studies that have compared TNBC versus nonTNBC in a homogeneous population. Comparison of these groups may help to identify genes that are key hallmarks in TNBC patients. Objective: To analyze the expression profile of TNBC versus nonTNBC in a homogeneous population from northwestern Mexico, in order to find distinctive biological pathways characteristics to TNBC. Methods: A prospective study was conducted involving a total of 50 patients (25 TNBC and 25 nonTNBC) undergoing neoadjuvant chemotherapy (NAC) for breast cancer. Both groups were similar in mean age at diagnosis (51 vs 47 years), mean of glucose levels (107 mg/dl vs 104 mg/dl) and BMI (28 vs 29) for TNBC and nonTNBC respectively. Core biopsies were obtained for histological diagnosis and gene expression, total RNA was isolated and expression profiling performed. Some of the differentially expressed genes were selected and validated by qPCR Results: Seventy percentage of the population presented BMI > 25. We identified a genomic profile expression composed of 40 genes associated with TNBC phenotype. Out of 40 genes, 9 were overexpressed (FOXC1, PRKX/PRKY, UGT8, BCL11A, HMGA1, LPIN1, FAM171A1, HAPLN3, y ANKRD11) and 31 under-expressed. Interestingly, some of these genes were previously associated to breast cancer. HMGA1, PRKX and LPIN1 participate in the insulin metabolism, UGT8 in the sphingolipids metabolism, while two others are transcription factors associated with metastasis and poor prognosis (FOXC1) and tumor growth (BCL11A). Conclusions: To our knowledge this is the first study in Latin American woman reporting a genomic signature for TNBC strongly associated with aberrant metabolism itself, such as seen in obesity. Understanding cell metabolism may help to clarify the mechanism for tumor development and progression in TNBC patients. Citation Format: Santuario-Facio SK, Cardona-Huerta S, Perez-Paramo YX, Treviño V, Hernandez-Cabrera F, Rojas-Martinez A, Psdilla-Rivas G, Muñoz-Maldonado G, Barbosa-Quintana A, Barbosa-Quintana O, Garza-Guajardo R, Gonzalez-Guerrero JF, Martinez-Rodriguez JL, Ortiz-López R. Gene expression profile of triple negative breast cancer in patients highlight biomarkers involved in cell metabolism. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-20.
Published Version
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