Development of a predictive miRNA signature for breast cancer risk among high-risk women.
Development of a predictive miRNA signature for breast cancer risk among high-risk women.
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DOI：
10.18632/oncotarget.22750
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发表时间：
2017-12-22
期刊：
影响因子：
--
通讯作者：
Wood ME
中科院分区：
文献类型：
--
作者：
Farina NH;Ramsey JE;Cuke ME;Ahern TP;Shirley DJ;Stein JL;Stein GS;Lian JB;Wood ME
我们在个体水平上预测乳腺癌风险的能力存在重大局限性。循环microRNA（C-miRNA）已成为癌症检测的可测量生物标志物（液体活检）。我们评估了C-miRNAs的能力，以确定最有可能发展为乳腺癌的妇女，通过分析诊断前很久获得的血清中的miRNA。24例乳腺癌病例和对照（风险和年龄匹配）从参加UVM癌症中心高风险乳腺计划的妇女中确定。从血清中分离的RNA分析了超过2500种人miRNA。将miRNA表达数据输入逐步线性回归模型，以发现预测乳腺癌长期风险的多变量miRNA特征。鉴定了25种候选miRNA，其基于统计方法对病例和对照进行单独分类。在该队列中，在区分病例和对照（AUC 0.896，CI 0.804-0.988）的回归建模之后发现了改进的6-miRNA风险特征。当病例与对照对比时，提出并通过途径分析证实了聚集在一起的miRNA之间的功能关系。发现的6种miRNA风险特征可以区分最终患乳腺癌的高风险女性和无癌女性，改善了目前的风险评估模型。未来的研究将集中在此签名中的miRNAs的功能分析和更大队列中的测试。我们认为，联合签名对于预测癌症风险非常重要，值得在更大的独立临床队列中进一步筛选。
Significant limitations exist in our ability to predict breast cancer risk at the individual level. Circulating microRNAs (C-miRNAs) have emerged as measurable biomarkers (liquid biopsies) for cancer detection. We evaluated the ability of C-miRNAs to identify women most likely to develop breast cancer by profiling miRNA from serum obtained long before diagnosis. 24 breast cancer cases and controls (matched for risk and age) were identified from women enrolled in the High-Risk Breast Program at the UVM Cancer Center. Isolated RNA from serum was profiled for over 2500 human miRNAs. The miRNA expression data were input into a stepwise linear regression model to discover a multivariable miRNA signature that predicts long-term risk of breast cancer. 25 candidate miRNAs were identified that individually classified cases and controls based on statistical methodologies. A refined 6-miRNA risk-signature was discovered following regression modeling that distinguishes cases and controls (AUC0.896, CI 0.804-0.988) in this cohort. A functional relationship between miRNAs that cluster together when cases are contrasted against controls was suggested and confirmed by pathway analyses. The discovered 6 miRNA risk-signature can discriminate high-risk women who ultimately develop breast cancer from those who remain cancer-free, improving current risk assessment models. Future studies will focus on functional analysis of the miRNAs in this signature and testing in larger cohorts. We propose that the combined signature is highly significant for predicting cancer risk, and worthy of further screening in larger, independent clinical cohorts.
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影响因子：
3.7
作者：
Creighton CJ;Benham AL;Zhu H;Khan MF;Reid JG;Nagaraja AK;Fountain MD;Dziadek O;Han D;Ma L;Kim J;Hawkins SM;Anderson ML;Matzuk MM;Gunaratne PH
通讯作者：
Gunaratne PH
影响因子：
6.6
作者：
Kodahl AR;Lyng MB;Binder H;Cold S;Gravgaard K;Knoop AS;Ditzel HJ
通讯作者：
Ditzel HJ
DOI：
10.1186/bcr3428
发表时间：
2013-05-24
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Godfrey AC;Xu Z;Weinberg CR;Getts RC;Wade PA;DeRoo LA;Sandler DP;Taylor JA
通讯作者：
Taylor JA
中国患者贲门腺癌 microRNA 分析
影响因子：
--
作者：
Gao, Shegan;Zhou, Fuyou;Feng, Xiaoshan
通讯作者：
Feng, Xiaoshan
影响因子：
6.4
作者：
Larne, Olivia;Martens-Uzunova, Elena;Ceder, Yvonne
通讯作者：
Ceder, Yvonne