Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland.
UMass Memorial Heart & Vascular Center, University of Massachusetts Medical School, The Albert Sherman Center, 7th Floor West, AS7-1051, 368 Plantation St, Worcester, MA, 01605-4319, USA.
BMC Cancer. 2019 May 10;19(1):436. doi: 10.1186/s12885-019-5636-y.
Breast cancer is the leading cause of cancer related death in women, with metastasis the principle cause of mortality. New non-invasive prognostic markers are needed for the early detection of metastasis, facilitating treatment decision optimisation. MicroRNA (miRNA) are small, non-coding RNAs regulating gene expression and involved in many cellular processes, including metastasis. As biomarkers, circulating miRNAs (in blood) hold great promise for informing diagnosis or monitoring treatment responses.
Plasma extracted RNA from age matched local Luminal A (n = 4) or metastatic disease (n = 4) were profiled using Next Generation Sequencing. Selected differentially expressed miRNA were validated on a whole blood extracted miRNA cohort [distant metastatic disease (n = 22), local disease (n = 31), healthy controls (n = 21)]. Area Under the Curve (AUC) in Receiver Operating Characteristic (ROC) analyses was performed.
Of 4 miRNA targets tested (miR-181a, miR-329, miR-331, miR-195), mir-331 was significantly over-expressed in patients with metastatic disease, compared to patients with local disease (p < 0.001) or healthy controls (p < 0.001). miR-195 was significantly under-expressed in patients with metastatic disease, compared to patients with local disease (p < 0.001) or healthy controls (p = 0.043). In combination, miR-331 and miR-195 produced an AUC of 0.902, distinguishing metastatic from local breast cancer.
We identified and validated two circulating miRNAs differentiating local Luminal A breast cancers from metastatic breast cancers. Further investigation will reveal the molecular role of these miRNAs in metastasis, and determine if they are subtype specific. This work demonstrates the ability of circulating miRNA to identify metastatic disease, and potentially inform diagnosis or treatment effectiveness.
乳腺癌是女性癌症相关死亡的主要原因，转移是导致死亡的主要原因。需要新的非侵入性预后标志物来早期检测转移，从而优化治疗决策。微小 RNA（miRNA）是调节基因表达的小非编码 RNA，参与包括转移在内的许多细胞过程。作为生物标志物，循环 miRNA（血液中）为提供诊断或监测治疗反应提供了巨大的潜力。
使用下一代测序对年龄匹配的局部 Luminal A（n=4）或转移性疾病（n=4）的血浆提取 RNA 进行分析。在全血提取 miRNA 队列上验证了选定的差异表达 miRNA[远处转移性疾病（n=22）、局部疾病（n=31）、健康对照（n=21）]。在接收器操作特征（ROC）分析中进行了曲线下面积（AUC）分析。
在测试的 4 个 miRNA 靶标（miR-181a、miR-329、miR-331、miR-195）中，与局部疾病患者（p<0.001）或健康对照（p<0.001）相比，转移性疾病患者中 mir-331 的表达明显升高。与局部疾病患者（p<0.001）或健康对照（p=0.043）相比，转移性疾病患者中 miR-195 的表达明显降低。联合使用 miR-331 和 miR-195 可区分转移性和局部乳腺癌，AUC 为 0.902。
我们鉴定并验证了两种区分局部 Luminal A 乳腺癌和转移性乳腺癌的循环 miRNA。进一步的研究将揭示这些 miRNA 在转移中的分子作用，并确定它们是否具有亚型特异性。这项工作证明了循环 miRNA 识别转移性疾病的能力，并可能为诊断或治疗效果提供信息。
