Investigation of circulating miR-182-3p, miR -382-3p and miR -93, miR -142-3p involved in tamoxifen resistance and sensitivity in luminal-subtype breast cancer patients: a case-control study.

Abstract

Breast cancer (BC) commonly expresses estrogen receptors (ERs); hence, endocrine therapy targeting ERs is considered an effective treatment. Tamoxifen (TAM) resistance is an essential clinical complication leading to cancer progression and metastasis. This study investigated MicroRNAs (miRNAs) potentially implicated in drug resistance (miR-182-3p, miR-382-3p) or sensitivity (miR-93, miR- 142- 3p). This study aimed to provide new insights into serum microRNA expression profiles in BC. This case-control study included patients with luminal-A BC who received TAM for approximately one year. The case and control groups included 40 patients with or without local recurrence or metastasis. The expression levels of miR-182-3p, miR-382-3p, miR-93, and miR-142-3p in plasma samples were measured using real-time PCR with target-specific primers. The multivariate model of miR-93 (p = 0.0002), miR-182-3p (p = 0.0002), and miR-382-3p (p = 0.0028) demonstrated higher predictive power for TAM resistance. The only significant association was observed between miR-382-3p expression and lymphovascular invasion (LVI) (p = 0.0314). Moreover, lower expression levels of miR-93 and miR-382-3p were observed in the TAM-sensitive group compared to the TAM-resistant counterparts (p = 0.0002 and p = 0.0028, respectively). In contrast, the expression level of miR-182-3p was significantly higher in the TAM-sensitive group compared to the TAM-resistant group (p = 0.0002). receiver operating characteristic (ROC) curve analysis also indicated the expression of miR-182-3p (p < 0.001; area under curve (AUC): 0.753), miR-382-3p (p = 0.0028; AUC: 0.697), and miR-93 (p < 0.001; AUC: 0.762) as predictive markers for TAM resistance. Multivariate models based on miR-182-3p, miR-382-3p, and miR-93 can predict the response to hormone therapy. Measuring these miRNAs is also recommended for patients with luminal-subtype BC undergoing TAM therapy.