Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute Detroit, Michigan, USA.
Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute Detroit, Michigan, USA.
Am J Transl Res. 2014 Jul 18;6(4):384-90. eCollection 2014.
Brain metastases from primary breast cancer are difficult to treat and associated with poor prognosis. Our understanding of the molecular basis for the development of such cancers is sparse. We hypothesized that the pro-metastatic microRNA-10b (miR-10b) plays a role in breast cancer brain metastasis. The study cohort comprised of twenty patients with breast cancer and brain metastasis as well as ten control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. All cases were microscopically reviewed to select tumor blocks with >50% tumor cells. RNA was extracted from formalin fixed paraffin embedded (FFPE) tumor tissue blocks. Expression of miR-10b was analyzed using qRT-PCR. The relevance of miR-10b expression was also tested using human breast cancer cell lines. An increased expression of miR-10b was noted in the primary breast cancer specimens of patients who subsequently developed brain metastasis, compared to those who did not. miR-10b also increased the invasive potential of breast cancer cells in vitro. Wilcoxon signed rank test revealed a statistically significant difference between the paired tumors from breast cancers and brain metastasis (p <0.001). Increased expression of miR-10b appears to be associated with breast cancer brain metastasis. These findings are clinically relevant since miR-10b could serve as a prognostic and/or therapeutic target for anti-metastatic therapy. Identifying molecular signatures of primary breast cancers which have a propensity for brain metastasis is critical for designing novel therapies to counter the development of brain metastasis in patients diagnosed with breast cancer.
原发性乳腺癌脑转移难以治疗且预后不良。我们对这类癌症发生的分子基础的了解还很有限。我们假设促转移 microRNA-10b（miR-10b）在乳腺癌脑转移中发挥作用。研究队列包括 20 名患有乳腺癌和脑转移的患者以及 10 名具有年龄、分期和随访相匹配的无脑转移乳腺癌的对照患者。所有病例均经显微镜检查选择肿瘤块中>50%的肿瘤细胞。从福尔马林固定石蜡包埋（FFPE）肿瘤组织块中提取 RNA。使用 qRT-PCR 分析 miR-10b 的表达。还使用人乳腺癌细胞系测试了 miR-10b 表达的相关性。与未发生脑转移的患者相比，随后发生脑转移的患者原发性乳腺癌标本中 miR-10b 的表达增加。miR-10b 还增加了乳腺癌细胞在体外的侵袭潜能。Wilcoxon 符号秩检验显示乳腺癌和脑转移的配对肿瘤之间存在统计学显著差异（p<0.001）。miR-10b 的表达增加似乎与乳腺癌脑转移有关。这些发现具有临床意义，因为 miR-10b 可以作为抗转移治疗的预后和/或治疗靶标。确定具有脑转移倾向的原发性乳腺癌的分子特征对于设计新的治疗方法以对抗诊断为乳腺癌的患者脑转移的发展至关重要。
