Department of Oncological Surgery and Gynecological Oncology, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Department of Radiology, The Oncology Institute "Prof. Dr. Ion Chiricuță", 400015 Cluj-Napoca, Romania.
Medicina (Kaunas). 2022 Oct 20;58(10):1494. doi: 10.3390/medicina58101494.
Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best characterize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting drug resistance. We aimed to assess the association of miR-375-3p, miR-210-3p and let-7e-5p in breast cancer tissues with pathological response to neoadjuvant therapy (NAT) and clinicopathological data. : Sixty female patients diagnosed with invasive breast cancer at The Oncology Institute "Ion Chiricuță", Cluj-Napoca, Romania (IOCN) were included in this study. Before patients received any treatment, fresh breast tissue biopsies were collected through core biopsy under echographic guidance and processed for total RNA extraction and miRNA quantification. The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) database was used as an independent external validation cohort. miR-375-3p expression was associated with more differentiated tumours, hormone receptor presence and lymphatic invasion. According to the Miller-Payne system, a higher miR-375-3p expression was calculated for patients that presented with intermediate versus (vs.) no pathological response. Higher miR-210-3p expression was associated with an improved response to NAT in both Miller-Payne and RCB evaluation systems. Several druggable mRNA targets were correlated with miR-375-3p and miR-210-3p expression, with upstream analysis using the IPA knowledge base revealing a list of possible chemical and biological targeting drugs. Regarding let-7e-5p, no significant association was noticed with any of the analysed clinicopathological data. Our results suggest that tumours with higher levels of miR-375-3p are more sensitive to neoadjuvant therapy compared to resistant tumours and that higher miR-210-3p expression in responsive tumours could indicate an excellent pathological response.
预测治疗反应仍然是治疗乳腺癌的持续挑战,特别是确定能够最好地描述耐药肿瘤的分子组织标志物。微小 RNA(miRNA),作为肿瘤表型的主要调节因子,可能是预测药物耐药性的有帮助的候选者。我们旨在评估乳腺癌组织中 miR-375-3p、miR-210-3p 和 let-7e-5p 与新辅助治疗(NAT)的病理反应以及临床病理数据的相关性。
本研究纳入了 60 名在罗马尼亚克卢日-纳波卡肿瘤研究所(IOCN)诊断为浸润性乳腺癌的女性患者。在患者接受任何治疗之前,通过超声引导下的核心活检采集新鲜的乳腺癌组织活检,并进行总 RNA 提取和 miRNA 定量。癌症基因组图谱乳腺癌浸润性癌(TCGA-BRCA)数据库被用作独立的外部验证队列。
miR-375-3p 的表达与分化程度较高的肿瘤、激素受体存在和淋巴管浸润有关。根据 Miller-Payne 系统,在存在中间而非(vs.)无病理反应的患者中,计算出较高的 miR-375-3p 表达。在 Miller-Payne 和 RCB 评估系统中,较高的 miR-210-3p 表达与 NAT 反应的改善相关。miR-375-3p 和 miR-210-3p 表达与几个可药物靶向的 mRNA 靶标相关,使用 IPA 知识库进行上游分析显示出一系列可能的化学和生物靶向药物的列表。关于 let-7e-5p,与任何分析的临床病理数据均无显著相关性。
我们的研究结果表明,与耐药肿瘤相比,miR-375-3p 水平较高的肿瘤对新辅助治疗更敏感,而对反应性肿瘤中 miR-210-3p 表达的增加可能预示着出色的病理反应。