Genomics Sciences Program, Autonomous University of Mexico City, Mexico City 03100, Mexico.
Molecular Biomedicine Program and Biotechnology Network, Instituto Politécnico Nacional, Mexico City 07320, Mexico.
Oncol Rep. 2019 Jun;41(6):3527-3534. doi: 10.3892/or.2019.7102. Epub 2019 Apr 5.
Cancer patients who better benefit from neoadjuvant chemotherapy (NeoCh) are those who achieve a successful pathological complete response (pCR) represented by the absence of residual disease. Unfortunately, no highly sensitive and specific tumor biomarkers for predicting the clinical response to NeoCh have yet been defined. The aim of the present study was to ascertain whether miR‑145‑5p could discriminate between pCR and no‑pCR in triple‑negative breast cancer patients that received a cisplatin/doxorubicin‑based neoadjuvant treatment. miR‑145‑5p expression was determined in breast tumors by quantitative RT‑PCR. Our data showed that miR‑145‑5p had a significant low expression (P<0.005) in patients that achieved pCR in comparison to the non‑responder group. Kaplan Meier analysis indicated that low levels of miR‑145‑5p were associated with increased disease‑free survival. In addition, receiver operating characteristic (ROC) curve analysis suggested that miR‑145‑5p is a good predictor of pCR (P<0.003, AUC=0.7899, 95% CI, 0.6382‑0.9416). Quantitative RT‑PCR expression analysis also revealed that miR‑145‑5p was downregulated in four breast cancer cell lines relative to normal cells. To study the functions of miR‑145‑5p, its expression was restored in triple‑negative MDA‑MB‑231 cells and its effects in cell proliferation were evaluated by MTT assays and in apoptosis using Annexin V experiments. Data revealed that ectopic expression of miR‑145‑5p resulted in a significant inhibition of cell proliferation and also induced apoptosis. Moreover, miR‑145‑5p led to sensitization of breast cancer cells to cisplatin therapy. In addition, western blot assays indicated that miR‑145‑5p downregulated the TGFβR2 protein. In conclusion, miR‑145‑5p could be a potential biomarker of clinical response to NeoCh in triple‑negative breast cancer. Functionally miR‑145‑5p may regulate cell proliferation, at least in part, by targeting TGFβR2.
癌症患者从新辅助化疗（NeoCh）中获益更多的是那些达到成功病理完全缓解（pCR）的患者，其特征是没有残留疾病。不幸的是，目前还没有用于预测NeoCh 临床反应的高度敏感和特异的肿瘤生物标志物。本研究旨在确定 miR-145-5p 是否可以区分接受顺铂/多柔比星为基础的新辅助治疗的三阴性乳腺癌患者的 pCR 和非 pCR。通过定量 RT-PCR 确定乳腺癌肿瘤中的 miR-145-5p 表达。我们的数据显示，与无反应组相比，达到 pCR 的患者 miR-145-5p 的表达明显较低（P<0.005）。Kaplan-Meier 分析表明，miR-145-5p 水平低与无病生存率增加相关。此外，接收器操作特征（ROC）曲线分析表明，miR-145-5p 是 pCR 的良好预测因子（P<0.003，AUC=0.7899，95%CI，0.6382-0.9416）。定量 RT-PCR 表达分析还显示，与正常细胞相比，miR-145-5p 在四种乳腺癌细胞系中下调。为了研究 miR-145-5p 的功能，将其在三阴性 MDA-MB-231 细胞中表达恢复，并通过 MTT 测定评估其对细胞增殖的影响，通过 Annexin V 实验评估其对细胞凋亡的影响。数据显示，miR-145-5p 的异位表达导致细胞增殖显著抑制，并诱导细胞凋亡。此外，miR-145-5p 导致乳腺癌细胞对顺铂治疗的敏感性增加。此外，western blot 检测表明，miR-145-5p 下调 TGFβR2 蛋白。总之，miR-145-5p 可能是三阴性乳腺癌 NeoCh 临床反应的潜在生物标志物。功能上，miR-145-5p 可能通过靶向 TGFβR2 来调节细胞增殖，至少部分如此。
