Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

作者：Weige Tan, Gehao Liang, Xinhua Xie, Wen G. Jiang, Luyuan Tan, Andrew J. Sanders, Zihao Liu, Yun Ling, Wenjing Zhong, Zhenluan Tian, Wanyi Lin, Chang Gong · 发表于：The Oncologist · 年份：2019 · DOI：10.1634/theoncologist.2018-0697 · 被引用次数：27 · 研究领域：Cancer Cells and Metastasis、MicroRNA in disease regulation、Cancer Risks and Factors

Abstract Background The molecular phenotype of circulating tumor cells (CTCs) was associated with clinical outcome of patients with breast cancer. CTCs isolated from patients with metastatic breast cancer (MBC) display a unique microRNA (miRNA) expression profile. The aim of this study was to enhance the prognostic accuracy of the CTC phenotype in patients with MBC, by incorporating miRNA into a combined prediction model. Subjects, Materials, and Methods CTCs were detected by CellSearch and enriched by magnetic cell sorting. miRNA deep sequencing and quantitative polymerase chain reaction were used to screen and verify potentially CTC-specific miRNA candidates. Patients with MBC were enrolled from two independent cohorts, and overall survival (OS) and chemotherapy response were analyzed. Results We screened and identified that miR-106b was an upregulated molecule in patients with MBC with CTC ≥5/7.5 mL (n = 16) compared with patients with CTC = 0/7.5 mL (n = 16) and healthy donors (n = 8). The expression of CTC-specific miR-106b correlated with vimentin and E-cadherin in CTC and acted as an independent factor for predicting OS (hazard ratio 2.157, 95% confidence interval [CI] 1.098–4.239, p = .026). Although CTC-specific miR-106b, E-cadherin, and vimentin showed a prognostic potential independently, the prognostic performance for OS based on the combination of three markers was significantly enhanced in Cohort 1 (area under the curve [AUC] 0.752, 95% CI 0.658–0.847, n = 128) ...