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学科主题: 临床医学
题名:
A circulating miRNA signature as a diagnostic biomarker for non-invasive early detection of breast cancer
作者: Zhang, Lei1; Xu, Ye2; Jin, Xingyu3; Wang, Zengwu4; Wu, Yidi1; Zhao, Deyao1; Chen, Gang5; Li, Deyu5; Wang, Xiaoxia1; Cao, Huiqing1; Xie, Yuntao2; Liang, Zicai1
关键词: Circulating miRNA ; Serum direct detection ; Breast cancer ; Diagnosis
刊名: BREAST CANCER RESEARCH AND TREATMENT
发表日期: 2015-11-01
DOI: 10.1007/s10549-015-3591-0
卷: 154, 期:2, 页:423-434
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: BLOOD-BASED MARKERS ; SCREENING MAMMOGRAPHY ; MICRORNA EXPRESSION ; HEPATOCELLULAR-CARCINOMA ; SERUM ; TUMOR ; CELLS ; IDENTIFICATION ; ACCURACY ; TARGETS
英文摘要:

Novel, non-invasive biomarkers to diagnose breast cancer with high sensitivity and specificity are greatly desired. Circulating microRNAs (miRNAs) show potential for breast cancer detection, but the existing results appear to be mixed. Using microscale serum, we established a novel serum-direct multiplex detection assay based on RT-PCR (SdM-RT-PCR). Ninety-three miRNAs dysregulated or with functions in breast cancer were selected as candidates, and additional 3 miRNAs were chosen as endogenous controls. We first conducted miRNA profiling of these 96 miRNAs by SdM-RT-PCR using the sera of 25 breast cancer patients at diagnosis prior to treatment and 20 age-matched healthy controls. miRNAs showing significantly different expression levels between patients and controls were further analyzed using a logistic regression model. A miRNA signature was validated in an independent set of 128 serum samples composed of 76 breast cancer patients and 52 healthy controls. In the discovery stage, we identified 23 miRNAs as significantly dysregulated in breast cancer patients compared with healthy controls. Of these, 10 miRNAs were previously identified as dysregulated in breast cancer; 14 miRNAs remained significant after P-values were adjusted by both correction methods. Principal component analysis and hierarchical clustering of these miRNAs separated patients from controls. Furthermore, the 3-miRNA signature (miR-199a, miR-29c, and miR-424) with the highest diagnostic accuracy for distinguishing breast cancer patients from controls by ROC curve analysis (AUC = 0.888) was successfully confirmed in the validation set (AUC = 0.901). Our data demonstrate that the SdM-RT-PCR assay is an effective breast cancer profiling method that utilizes very small volumes and is compatible with Biobank. Furthermore, the identified 3-miRNA signature is a promising circulating biomarker for breast cancer diagnosis.

语种: 英语
所属项目编号: 2012AA022501 ; 81170097 ; 81373070 ; BK2011381
项目资助者: National High-Tech R&amp ; D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of Jiangsu ; 985 Project of Peking University
WOS记录号: WOS:000365188600020
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62890
Appears in Collections:北京大学临床肿瘤学院_乳腺癌预防治疗中心_期刊论文

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作者单位: 1.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China
2.Peking Univ, Canc Hosp & Inst, Breast Ctr, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China
3.Suzhou Ribo Life Sci Co Ltd, Suzhou, Jiangsu, Peoples R China
4.Beijing Fuwai Hosp, Natl Ctr Cardiovasc Dis, Div Prevent & Community Hlth, Beijing, Peoples R China
5.Kunshan Ind Technol Res Inst, siRNA Biotechnol Res Inst, Suzhou, Jiangsu, Peoples R China

Recommended Citation:
Zhang, Lei,Xu, Ye,Jin, Xingyu,et al. A circulating miRNA signature as a diagnostic biomarker for non-invasive early detection of breast cancer[J]. BREAST CANCER RESEARCH AND TREATMENT,2015,154(2):423-434.
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