Identification of BRCA1/2 mutation female carriers using circulating microRNA profiles.
Identification of BRCA1/2 mutation female carriers using circulating microRNA profiles.
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DOI：
10.1038/s41467-023-38925-4
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发表时间：
2023-06-08
影响因子：
16.6
通讯作者：
Chowdhury, Dipanjan
中科院分区：
文献类型：
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作者：
Elias, Kevin;Smyczynska, Urszula;Stawiski, Konrad;Nowicka, Zuzanna;Webber, James;Kaplan, Jakub;Landen, Charles;Lubinski, Jan;Mukhopadhyay, Asima;Chakraborty, Dona;Connolly, Denise C.;Symecko, Heather;Domchek, Susan M.;Garber, Judy E.;Konstantinopoulos, Panagiotis;Fendler, Wojciech;Chowdhury, Dipanjan
识别生殖系BRCA 1/2突变携带者对于降低乳腺癌和卵巢癌的风险至关重要。为了获得基于血清miRNA的诊断测试，我们使用了来自6个国际队列的653名健康女性的样本，包括350名（53.6%）BRCA 1/2突变和303名（46.4%）BRCA 1/2野生型。所有人在采样前和采样后至少12个月都没有癌症。RNA测序后进行差异表达分析，鉴定出19种与BRCA突变显著相关的miRNA，其中10种最终用于分类：hsa-miR-20b-5p、hsa-miR-19b-3p、hsa-let-7b-5p、hsa-miR-320b、hsa-miR-139-3p、hsa-miR-30d-5p、hsa-miR-17-5p、hsa-miR-182-5p、hsa-miR-421，hsa-miR-375-3p。在独立验证队列中，最终逻辑回归模型的受试者工作特征曲线下面积为0.89（95%CI：0.87-0.93），灵敏度为93.88%，特异性为80.72%。突变基因，绝经状态或有先发制人卵巢切除术不影响分类性能。循环microRNA可用于识别癌症高风险患者的BRCA 1/2突变，为降低筛查成本提供了机会。已知BRCA 1/2突变会增加乳腺癌和卵巢癌的风险，但健康个体的携带者状态在没有基因检测的情况下是未知的。在这里，作者创建了一个循环miRNA签名来预测健康个体的BRCA 1/2携带者状态，以帮助基因检测的决策过程。
Identifying germline BRCA1/2 mutation carriers is vital for reducing their risk of breast and ovarian cancer. To derive a serum miRNA-based diagnostic test we used samples from 653 healthy women from six international cohorts, including 350 (53.6%) with BRCA1/2 mutations and 303 (46.4%) BRCA1/2 wild-type. All individuals were cancer-free before and at least 12 months after sampling. RNA-sequencing followed by differential expression analysis identified 19 miRNAs significantly associated with BRCA mutations, 10 of which were ultimately used for classification: hsa-miR-20b-5p, hsa-miR-19b-3p, hsa-let-7b-5p, hsa-miR-320b, hsa-miR-139-3p, hsa-miR-30d-5p, hsa-miR-17-5p, hsa-miR-182-5p, hsa-miR-421, hsa-miR-375-3p. The final logistic regression model achieved area under the receiver operating characteristic curve 0.89 (95% CI: 0.87–0.93), 93.88% sensitivity and 80.72% specificity in an independent validation cohort. Mutated gene, menopausal status or having preemptive oophorectomy did not affect classification performance. Circulating microRNAs may be used to identify BRCA1/2 mutations in patients of high risk of cancer, offering an opportunity to reduce screening costs. BRCA1/2 mutations are known to increase risk of breast and ovarian cancer but carrier status in healthy individuals is unknown without genetic testing. Here, the authors created a circulating miRNA signature to predict BRCA1/2 carrier status in healthy individuals to aid the decision process on genetic testing.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
7.7
作者：
Choi YE;Pan Y;Park E;Konstantinopoulos P;De S;D'Andrea A;Chowdhury D
通讯作者：
Chowdhury D
影响因子：
16
作者：
Moskwa P;Buffa FM;Pan Y;Panchakshari R;Gottipati P;Muschel RJ;Beech J;Kulshrestha R;Abdelmohsen K;Weinstock DM;Gorospe M;Harris AL;Helleday T;Chowdhury D
通讯作者：
Chowdhury D
双年度动态对比度增强的磁共振成像在BRCA1突变载体中乳腺癌下降。
DOI：
10.1158/1078-0432.ccr-18-0200
发表时间：
2019-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Guindalini RSC;Zheng Y;Abe H;Whitaker K;Yoshimatsu TF;Walsh T;Schacht D;Kulkarni K;Sheth D;Verp MS;Bradbury AR;Churpek J;Obeid E;Mueller J;Khramtsova G;Liu F;Raoul A;Cao H;Romero IL;Hong S;Livingston R;Jaskowiak N;Wang X;Debiasi M;Pritchard CC;King MC;Karczmar G;Newstead GM;Huo D;Olopade OI
通讯作者：
Olopade OI
DOI：
10.1073/pnas.0804549105
发表时间：
2008-07-29
影响因子：
11.1
作者：
Mitchell, Patrick S.;Parkin, Rachael K.;Tewari, Muneesh
通讯作者：
Tewari, Muneesh