Apollonova Vera, Plevako Daniil, Garanin Alexandr, Sidina Elena, Zabegina Lidia, Knyazeva Margarita, Smirnova Viktoria, Artemyeva Anna, Krivorotko Petr, Malek Anastasia
Breast Surgical Oncology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg 197758, Russia.
Authors contributed equally.
Cancer Drug Resist. 2023 Sep 1;6(3):596-610. doi: 10.20517/cdr.2023.19. eCollection 2023.
Neo-adjuvant chemotherapy is a common approach for the complex treatment of breast cancer (BC) and paclitaxel (PTX) is frequently included in the therapeutic regimen. However, the effect of PTX-based treatment is hard to predict precisely based on routinely used markers. As microRNAs are considered a new promising class of biomarkers, the link between miRNA expression and PTX resistance of BC cells needs to be well investigated. This study aimed at the identification of miRNAs associated with responses of BC cells to PTX. Intrinsic PTX sensitivity and miRNA profiling were assayed in five BC cell lines to identify candidate miRNAs. Selected miRNA (n. 15) expressions were analyzed by real-time-quantitative polymerase chain reaction (RT-qPCR) in BC tissue samples (n. 31) obtained from a diagnostic biopsy. Results were analyzed in the context of the effect of two cycles of PTX and the effect of the completed scheme of neoadjuvant therapy. The study's design facilitated the evaluation of the effect of PTX on cells and the identification of features of the microRNA expression profiles associated exclusively with sensitivity to this drug. miR-186 and miR-7 expression in BC tissues was higher in patients with better outcomes of PTX-based neoadjuvant therapy. High expressions of miR-186 and miR-7 are associated with good response to PTX, whereas their low expressions may be associated with resistance to PTX in BC, indicating the possibility of developing innovative test systems for the prediction of the PTX response, which can be used before the start of neo-adjuvant chemotherapy for BC.
新辅助化疗是乳腺癌(BC)综合治疗的常用方法,紫杉醇(PTX)常被纳入治疗方案。然而,基于常规使用的标志物很难精确预测基于PTX的治疗效果。由于微小RNA被认为是一类新的有前景的生物标志物,因此需要深入研究miRNA表达与BC细胞对PTX耐药性之间的联系。本研究旨在鉴定与BC细胞对PTX反应相关的miRNA。在五种BC细胞系中检测内在PTX敏感性和miRNA谱,以鉴定候选miRNA。通过实时定量聚合酶链反应(RT-qPCR)分析从诊断性活检获得的BC组织样本(n = 31)中选定的miRNA(n = 15)表达。在两个周期的PTX效果和新辅助治疗完整方案的效果背景下分析结果。该研究设计有助于评估PTX对细胞的作用,并鉴定仅与对该药物敏感性相关的微小RNA表达谱特征。在基于PTX的新辅助治疗效果较好的患者中,BC组织中miR-186和miR-7的表达较高。miR-186和miR-7的高表达与对PTX的良好反应相关,而它们的低表达可能与BC对PTX的耐药性相关,这表明有可能开发创新的检测系统来预测PTX反应,可在BC新辅助化疗开始前使用。