Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis
Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis
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DOI：
10.1093/carcin/bgw008
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发表时间：
2016-05-01
期刊：
影响因子：
4.7
通讯作者：
Burwinkel, Barbara
中科院分区：
文献类型：
--
作者：
Madhavan, Dharanija;Peng, Cike;Burwinkel, Barbara
转移性乳腺癌的预后生物标志物缺乏。我们已经鉴定了一组可在血浆中测量的用于早期检测转移的miRNAs，这也是独立于临床因素在MBC中进行预测的有效方法。转移是乳腺癌（BC）患者高发病率和死亡率的主要原因。鉴定可以常规监测以预测BC患者转移的发生和转移性乳腺癌（MBC）患者的预后的标志物将增加其中位生存期。在这项研究中，40例MBC患者的血浆miRNAs通过TaqMan低密度阵列进行了分析，并鉴定了具有预后能力的miRNAs。候选人最初在237名MBC患者的样本中进行了验证，随后在来自BC患者的独立研究队列的335个样本中进行了验证。16种miRNA被确定与总生存率显著相关，并被称为预后miRNA面板模板（PROMPT）。这些包括miR-141、miR-144、miR-193b、miR-200a、miR-200b、miR-200c、miR-203、miR-210、miR-215、miR-365、miR-375、miR-429、miR-486-5p、miR-801、miR-1260和miR-1274a。此外，这些miRNAs中的11种也与无进展生存期相关。它们的预后意义在来自BC患者的第二研究队列的样本中得到进一步证实。此外，发现miR-200 a、miR-200 b、miR-200 c、miR-210、miR-215和miR-486- 5 p与BC患者临床诊断前2年的转移发生显著相关。因此，我们已经鉴定了一组miRNA，包括促进转移的miR-200家族和miR-203，以及致癌和肿瘤抑制的miRNA，它们可以作为MBC的预后标志物和BC转移的早期检测标志物。
There is a paucity of prognostic biomarkers for metastatic breast cancer. We have identified a panel of miRNAs that can be measured in plasma for early detection of metastasis, which is also effective for prognostication independently from clinical factors in MBC.Metastasis is the principal cause of high morbidity and mortality among breast cancer (BC) patients. Identification of markers that can be routinely monitored to predict onset of metastasis in BC patients and prognosis of metastatic breast cancer (MBC) patients would increase their median survival. In this study, plasma miRNAs of 40 MBC patients were profiled by TaqMan low density arrays and miRNAs with prognostic capacity were identified. The candidates were validated initially in the samples of 237 MBC patients and subsequently in 335 samples from an independent study cohort of BC patients. Sixteen miRNAs were established to be significantly associated with overall survival, and were termed as prognostic miRNA panel template (PROMPT). These included miR-141, miR-144, miR-193b, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-215, miR-365, miR-375, miR-429, miR-486-5p, miR-801, miR-1260 and miR-1274a. Additionally, 11 of these miRNAs were also associated with progression-free survival. Their prognostic significance was further confirmed in samples from a second study cohort of BC patients. In addition, miR-200a, miR-200b, miR-200c, miR-210, miR-215 and miR-486-5p were found to be significantly associated with onset of metastasis up to 2 years prior to clinical diagnosis in BC patients. We have thus identified panels of miRNAs, which include metastasis promoting miR-200 family and miR-203, as well as oncogenic and tumor-suppressive miRNAs, that can serve as prognostic markers for MBC, and early detection markers of metastasis in BC.