Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Breast Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan.
PLoS One. 2019 Sep 4;14(9):e0222024. doi: 10.1371/journal.pone.0222024. eCollection 2019.
The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer.
在接受蒽环类药物和紫杉类药物预处理的转移性乳腺癌患者中,寻找预测对艾日布林反应性的生物标志物仍然是一个未满足的需求。在这里,我们建立了一种基于血清 microRNA(miRNA)的预测模型,用于预测接受艾日布林治疗后出现新的远处转移。在接受艾日布林治疗之前,采集转移性乳腺癌患者的血清样本,并通过 miRNA 微阵列进行全面评估。使用逻辑 LASSO 回归模型建立了用于估计艾日布林疗效的预测模型。从 147 名患者中采集了血清样本,其中 52 名患者在接受艾日布林单药治疗后至少出现了 1 个新的远处转移,95 名患者未出现新的远处转移。八种血清 miRNA(miR-4483、miR-8089、miR-4755-3p、miR-296-3p、miR-575、miR-4710、miR-5698 和 miR-3160-5p)的组合可预测新的远处转移的出现,曲线下面积为 0.79,敏感性为 0.69,特异性为 0.82。miR-8089 和 miR-5698 的血清水平与艾日布林治疗开始后的总生存显著相关。本研究表明,血清 miRNA 谱可能作为预测艾日布林反应性和转移性乳腺癌新远处转移发展的生物标志物。