Dampening enthusiasm for circulating microRNA in breast cancer.

Dampening enthusiasm for circulating microRNA in breast cancer.
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抑制了乳腺癌中循环microRNA的热情。

DOI:
10.1371/journal.pone.0057841
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Thompson CL
Thompson CL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Leidner RS;Li L;Thompson CL

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用于循环miRNA的高通量分析的全基因组平台(oligoarray或miR-Seq)为循环miRNA生物标志物的不可知发现提供了巨大的希望,作为乳腺癌检测的发展途径。通过协调以前15份报告的数据,我们发现以前的研究存在广泛的不一致性。这是否源于研究设计的差异,如样本来源或分析平台,尚不清楚。作为再现性实验,我们使用Illumina oligoarray生成了全基因组血浆miRNA数据集,并将其与使用相同样本量、底物和分析平台生成的药物学可用数据集进行比较。包括来自20名乳腺癌患者、20名乳房X线摄影筛查的对照以及20名手术切除后的乳腺癌患者和10名女性肺癌或结直肠癌患者的样本。在过滤来自血细胞的miRNAs和低丰度miRNAs后,(在超过10%的样品中检测不到),一组522种血浆miRNA仍然存在,其中46种在乳腺癌患者和健康对照之间差异表达(p<0.05),其中只有3例在切除术后病例中恢复到基线水平,并且是乳腺癌与肺癌或结直肠癌相比所特有的(miR-708*、miR-92 b * 和miR-568,先前未报道)。我们无法通过两个数据集之间的各种测量来证明重现性。这一发现,沿着广泛的不一致,在以前的研究中,强调需要更好地了解影响循环miRNA水平的因素作为先决条件,在这一领域的转化研究的进展。
Genome-wide platforms for high-throughput profiling of circulating miRNA (oligoarray or miR-Seq) offer enormous promise for agnostic discovery of circulating miRNA biomarkers as a pathway for development in breast cancer detection. By harmonizing data from 15 previous reports, we found widespread inconsistencies across prior studies. Whether this arises from differences in study design, such as sample source or profiling platform, is unclear. As a reproducibility experiment, we generated a genome-wide plasma miRNA dataset using the Illumina oligoarray and compared this to a publically available dataset generated using an identical sample size, substrate and profiling platform. Samples from 20 breast cancer patients, 20 mammography-screened controls, as well as 20 breast cancer patients after surgical resection and 10 female lung or colorectal cancer patients were included. After filtering for miRNAs derived from blood cells, and for low abundance miRNAs (non-detectable in over 10% of samples), a set of 522 plasma miRNAs remained, of which 46 were found to be differentially expressed between breast cancer patients and healthy controls (p<0.05), of which only 3 normalized to baseline levels in post-resection cases and were unique to breast cancer vs. lung or colorectal cancer (miR-708*, miR-92b* and miR-568, none previously reported). We were unable to demonstrate reproducibility by various measures between the two datasets. This finding, along with widespread inconsistencies across prior studies, highlight the need for better understanding of factors influencing circulating miRNA levels as prerequisites to progress in this area of translational research.
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