Quantitative assessment of miR34a as an independent prognostic marker in breast cancer.
Quantitative assessment of miR34a as an independent prognostic marker in breast cancer.
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DOI：
10.1038/bjc.2014.573
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发表时间：
2015-01-06
影响因子：
8.8
通讯作者：
Rimm, D. L.
中科院分区：
文献类型：
--
作者：
Agarwal, Seema;Hanna, J.;Sherman, M. E.;Figueroa, J.;Rimm, D. L.
MicroRNAs(MiRNAs)的异常表达与肿瘤的进展、发生和转移有关。MiR34a是一种miRNA，以前被描述为肿瘤抑制因子。在这里，我们使用定量原位杂交分析(QISH)评估miR34a在三个独立的乳腺癌队列中的表达，并确定其与乳腺癌疾病特异性死亡的相关性。Qish方法应用于三个独立的乳腺癌队列(队列1,461人，队列2,279人，队列3,795人)，使用5‘和3’地高辛标记的针对miR34a的LNA修饰探针，使用上述方案。以miR34a的自动定量分析(Aqua)分数测量每个患者的表达水平，并评估其与疾病特异性死亡风险的相关性。在队列1中，使用X-Tile软件确定疾病特异性生存的最佳切点，然后在AQUA评分的中值标准化后，将该切点应用于其他两个队列。在三个独立的乳腺癌队列中，miR34a的缺失与不良预后相关(队列1的未校正对数等级P=0.0188，队列2的对数等级P=0.0024，队列3的对数等级P=0.0455)。在所有三个队列中，miR34a的缺失能够在结节阴性患者中对疾病特异性存活率较低的患者进行分层，但在结节阳性人群中则不能。队列1(P=0.0381)和队列2(P=0.0468)的多因素COX比例风险分析显示，miR34a缺失与预后不良有关，与年龄、淋巴结状态、受体状态和肿瘤大小无关。肿瘤抑制基因miR34a的缺失，可以识别疾病特异性存活率较低的乳腺癌患者的亚群。这项研究与miR34a作为肿瘤抑制因子的临床前观察结果是一致的，并表明miR34a作为乳腺癌生物标记物可能有未来的价值。
Aberrant expression of microRNAs (miRNAs) is associated with cancer progression, initiation and metastasis. MiR34a is a miRNA that has been previously described as a tumour suppressor. Herein, we assess the expression of miR34a in three independent breast cancer cohorts using a quantitative in situ hybridisation assay (qISH) and determined its association with disease-specific death in breast cancer. The qISH method was applied to three independent primary breast cancer cohorts (Cohort 1 with 461, Cohort 2 with 279 and Cohort 3 with 795 patients) using 5′ and 3′ double DIG-labelled LNA-modified probe against miR34a using the protocol described previously. Level of expression measured as automated quantitative analysis (AQUA) score for miR34a was determined for each patient and assessed for association with risk of disease-specific death. An optimal cutpoint was determined using the X-tile software for disease-specific survival in Cohort 1 and this cutpoint was then applied to the other two cohorts after median normalisation of AQUA scores. Loss of miR34a is associated with poor outcome in three independent breast cancer cohorts (uncorrected log-rank P=0.0188 for Cohort 1, log-rank P=0.0024 for Cohort 2 and log-rank P=0.0455 for Cohort 3). In all three cohorts, loss of miR34a is able to stratify patients with poor disease-specific survival among node-negative patients, but not in node-positive population. Multivariate Cox proportional hazards analysis in Cohort 1 (P=0.0381) and Cohort 2 (P=0.0468) revealed that loss of miR34a is associated with poor outcome, independent of age, node status, receptor status and tumour size. Loss of the tumour suppressor, miR34a, identifies a subgroup of breast cancer patients with poor disease-specific survival. This study is consistent with the well-established preclinical observations for miR34a as a tumour suppressor and suggests that miR34a may have future value as a biomarker in breast cancer.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
3.8
作者：
Horne, Hisani N.;Sherman, Mark E.;Garcia-Closas, Montserrat;Pharoah, Paul D.;Blows, Fiona M.;Yang, Xiaohong R.;Hewitt, Stephen M.;Conway, Catherine M.;Lissowska, Jolanta;Brinton, Louise A.;Prokunina-Olsson, Ludmila;Dawson, Sarah-Jane;Caldas, Carlos;Easton, Douglas F.;Chanock, Stephen J.;Figueroa, Jonine D.
通讯作者：
Figueroa, Jonine D.
乳腺癌细胞迁移和侵袭过程中 miRNA:mRNA 相互作用的系统评估
影响因子：
7.4
作者：
Luo D;Wilson JM;Harvel N;Liu J;Pei L;Huang S;Hawthorn L;Shi H
通讯作者：
Shi H
影响因子：
6.2
作者：
Giltnane, Jennifer M.;Moeder, Christopher B.;Rimm, David L.
通讯作者：
Rimm, David L.
影响因子：
11.2
作者：
Kasinski AL;Slack FJ
通讯作者：
Slack FJ