MicroRNA in diagnosis and therapy monitoring of early-stage triple-negative breast cancer.

MicroRNA in diagnosis and therapy monitoring of early-stage triple-negative breast cancer.
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DOI:
10.1038/s41598-018-29917-2
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发表时间:
2018-08-02
期刊:
影响因子:
4.6
通讯作者:
Schrauder MG
Schrauder MG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kahraman M;Röske A;Laufer T;Fehlmann T;Backes C;Kern F;Kohlhaas J;Schrörs H;Saiz A;Zabler C;Ludwig N;Fasching PA;Strick R;Rübner M;Beckmann MW;Meese E;Keller A;Schrauder MG

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乳腺癌是一种具有不同分子亚型的异质性疾病,包括侵袭性亚型三阴性乳腺癌(TNBC)。我们比较了早期基底样型(细胞角蛋白CK5阳性)TNBC患者和年龄匹配的对照组的血液传播miRNA特征。在以铂为基础的新辅助化疗(NCT)之前和之后评估了TNBC患者的miRNAs。在使用微阵列对21例患者和21名对照进行探索性全基因组研究后,通过RT-qPCR在两个相同的实验室和一个新的队列中独立地验证了所识别的标记。我们在NCT前将TNBC患者的血液与对照组的血液进行了区分,敏感性为84%。最具诊断意义的miRNA是miR-126-5p(双尾t检验p值为1.4 × 10−5)。验证确认了所有测试的miRNAs的微阵列结果。比较癌症患者治疗前后的差异有321个(其中miR-34a,p值为1.2miRNA× × 10−23)。我们的结果还表明,在NCT过程中miRNA表达的变化可能具有预测病理完全应答(PCR)的潜力。总之,我们报告,从血液中测量miRNA的表达有助于基底细胞样TNBC的早期和微创诊断。我们还证明了NCT对miRNA的表达有显著影响。最后,我们表明,随着时间的推移,监测的血液传播miRNA图谱具有预测PCR的潜力。
Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4 × 10−5). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2 × 10−23). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR.
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影响因子: 4.1
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