Aboutalebi Vand Beilankouhi Elmira, Sanaat Zohreh, Hosseinpour Feizi Mohammad Ali, Mehdizadeh Amir, Safaralizadeh Reza
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 4. doi: 10.1007/s00210-024-03770-9.
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.
乳腺癌（BC）通常表达雌激素受体（ERs）；因此，针对ERs的内分泌治疗被认为是一种有效的治疗方法。他莫昔芬（TAM）耐药是导致癌症进展和转移的一种重要临床并发症。本研究调查了可能与耐药（miR-182-3p、miR-382-3p）或敏感性（miR-93、miR-142-3p）相关的微小RNA（miRNAs）。本研究旨在为BC患者血清微小RNA表达谱提供新的见解。这项病例对照研究纳入了接受TAM治疗约一年的腔面A型BC患者。病例组和对照组分别包括40例有或无局部复发或转移的患者。使用针对靶标的特异性引物通过实时PCR检测血浆样本中miR-182-3p、miR-382-3p、miR-93和miR-142-3p的表达水平。miR-93（p = 0.0002）、miR-182-3p（p = 0.0002）和miR-382-3p（p = 0.0028）的多变量模型对TAM耐药具有更高的预测能力。仅在miR-382-3p表达与淋巴管浸润（LVI）之间观察到显著关联（p = 0.0314）。此外，与TAM耐药组相比，TAM敏感组中miR-93和miR-382-3p的表达水平较低（分别为p = 0.0002和p = 0.0028）。相反，与TAM耐药组相比，TAM敏感组中miR-182-3p的表达水平显著更高（p = 0.0002）。受试者工作特征（ROC）曲线分析还表明，miR-182-3p（p < 0.001；曲线下面积（AUC）：0.753）、miR-382-3p（p = 0.0028；AUC：0.697）和miR-93（p < 0.001；AUC：0.762）的表达可作为TAM耐药的预测标志物。基于miR-182-3p、miR-382-3p和miR-93的多变量模型可以预测激素治疗的反应。对于接受TAM治疗的腔面亚型BC患者，也建议检测这些miRNAs。
