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

The oncologist

article

Weige Tan¹  Zhenluan Tian²  Wanyi Lin²  Chang Gong²  Gehao Liang²  Xinhua Xie⁴  Wenguo Jiang²  Luyuan Tan²  Andrew J. Sanders³  Zihao Liu²  Yun Ling²  Wenjing Zhong² 

[1] Breast Surgery Department, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University;Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, United Kingdom;Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University

关键词: Breast cancer;    Circulating tumor cells;    MicroRNA;    Prognosis;    Metastasis;   

DOI  :  10.1634/theoncologist.2018-0697

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

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) and further validated in Cohort 2 (AUC 0.726, 95% CI 0.595–0.856, n = 91). Besides, a combined model incorporating miR-106b was associated with therapy response. Conclusion The phenotypic assemblies of CTC incorporating miR-106b show enhanced prognostic accuracy of overall survival in patients with MBC. Implications for Practice In order to enhance the prognostic accuracy of the circulating tumor cell (CTC) phenotype in patients with metastatic breast cancer (MBC), this study screened and identified a CTC-specific microRNA (miRNA), miR-106b, as an upregulated molecule based on the comparison of miRNA profile between CTCs, primary tumors, and healthy blood donors. By incorporating miR-106b into a combined prediction model, the prognostic accuracy of the CTC phenotype for patients with MBC was greatly improved in both the training and validation cohorts. This work provides clinical evidence supporting the prognostic potential of CTC-specific miRNA for patients with MBC. These results indicate that developing CTC-specific miRNAs as new biomarkers will help to further optimize personalized therapy.

【 授权许可】

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