Patellongi Ilhamjaya, Amiruddin Alfiah, Massi Muhammad N, Islam Andi A, Pratama Muhammad Y, Sutandyo Noorwati, Latar Nani H M, Faruk Muhammad
Department of Physiology.
Doctoral Program of Biomedical Sciences.
Ann Med Surg (Lond). 2023 Jul 10;85(8):3806-3815. doi: 10.1097/MS9.0000000000001061. eCollection 2023 Aug.
The high mortality rate in breast cancer (BC) patients is generally due to metastases resistant to systemic therapy. Two causes of systemic therapy resistance in BC patients are circulating miRNAs-221 and miR-222, leading to improved BC cell proliferation, survival, and reduced cell apoptosis. This study investigated the miRNA expression changes associated with cancer cell resistance to tamoxifen therapy and is expected to be clinically meaningful before providing endocrine therapy to luminal-type BC patients who express them.
This case-control research included individuals with the luminal subtype of BC who had received tamoxifen medication for around one year. Furthermore, the case group contained 15 individuals with local recurrence or metastases, while the control group comprised 19 patients without local recurrence or metastases. Plasma miR-221/222 quantification was performed with real-time PCR using transcript-specific primers.
A significant difference was found in circulating miR-221 expression between cases and controls (=0.005) but not in miR-222 expression (=0.070). There were no significant differences between miR-221/222 expression, progesterone receptor, Ki67 protein levels, lymphovascular invasion, and stage. However, receiver operator characteristic curve analyses showed miR-221/222 expressions predictive of tamoxifen resistance (=0.030) with a sensitivity of 60.00 and a specificity of 83.33%.
The use of circulating miR-221/222 expression can predict relapse as well as resistance to tamoxifen treatment in BC patients, and their testing is recommended for luminal subtype BC patients who will undergo tamoxifen therapy to determine their risk of tamoxifen resistance early, increasing treatment effectiveness.
乳腺癌（BC）患者的高死亡率通常归因于对全身治疗耐药的转移灶。BC患者全身治疗耐药的两个原因是循环中的miRNAs - 221和miR - 222，它们会导致BC细胞增殖增加、存活能力增强以及细胞凋亡减少。本研究调查了与癌细胞对他莫昔芬治疗耐药相关的miRNA表达变化，预计在为表达这些miRNA的腔面型BC患者提供内分泌治疗之前具有临床意义。
本病例对照研究纳入了接受他莫昔芬治疗约一年的腔面亚型BC患者。此外，病例组包括15例局部复发或转移的患者，而对照组包括19例无局部复发或转移的患者。使用转录特异性引物通过实时PCR对血浆miR - 221/222进行定量分析。
病例组和对照组之间循环miR - 221表达存在显著差异（=0.005），但miR - 222表达无显著差异（=0.070）。miR - 221/222表达、孕激素受体、Ki67蛋白水平、淋巴管浸润和分期之间无显著差异。然而，受试者工作特征曲线分析显示miR - 221/222表达可预测他莫昔芬耐药（=0.030），敏感性为60.00，特异性为83.33%。
循环miR - 221/222表达可用于预测BC患者的复发以及对他莫昔芬治疗的耐药性，建议对将接受他莫昔芬治疗的腔面亚型BC患者进行检测，以便早期确定其对他莫昔芬耐药的风险，提高治疗效果。
