MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression.

MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression.
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DOI:
10.1093/carcin/bgv249
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发表时间:
2016-03
期刊:
影响因子:
4.7
通讯作者:
Wolff RK
Wolff RK
中科院分区:
医学2区
文献类型:
--
作者:
Slattery ML;Herrick JS;Pellatt DF;Stevens JR;Mullany LE;Wolff E;Hoffman MD;Samowitz WS;Wolff RK

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大约27%的miRNA通常在结肠组织中表达;当应用0.05的错误发现率时,其中超过86%在癌和正常组织之间失调。从正常到腺瘤到癌的miRNA表达因miRNA及其在人群中的表达频率而异。miRNA是一种非蛋白质编码的小RNA分子,通过转录后抑制mRNA翻译或mRNA降解来调节基因表达。我们研究了在结直肠癌、腺瘤和正常结肠粘膜中差异表达的miRNA。数据来自于在犹他州进行的基于人群的结直肠癌研究和Kaiser Permanente医疗保健计划。在含有2006个miRNA的Agilent Human miRNA Microarray V19.0上运行总共1893个癌/正常配对样品和290个腺瘤组织样品。我们检测了配对的癌/腺瘤/正常结肠组织样品之间miRNA表达的显著差异。在>80%的人的结肠组织中表达了少于600种miRNA;其中86.5%在癌和正常结肠粘膜之间具有统计学差异表达,错误发现率为0.05。这些差异表达的miRNAs中大约有一半显示出从正常组织到腺瘤组织再到癌组织的表达水平的进展。其他miRNA似乎在正常到腺瘤阶段发生改变,而其他miRNA仅在腺瘤到癌阶段或仅在正常到癌阶段发生改变。Agilent平台的评价显示出高度的重复性(r = 0.98),并且与NanoString平台合理一致。我们的数据表明,在结直肠癌患者的结直肠组织中,miRNA高度失调;随着组织从正常到腺瘤再到癌的进展,miRNA的破坏模式各不相同。
Roughly 27% of miRNAs are commonly expressed in colonic tissue; of these, over 86% are dysregulated between carcinoma and normal tissue when applying a false discovery rate of 0.05. MiRNA expression from normal to adenoma to carcinoma varied by miRNA and its frequency of expression in the population. MiRNAs are small, non-protein-coding RNA molecules that regulate gene expression either by post-transcriptionally suppressing mRNA translation or by mRNA degradation. We examine differentially expressed miRNAs in colorectal carcinomas, adenomas and normal colonic mucosa. Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma/normal-paired samples and 290 adenoma tissue samples were run on the Agilent Human miRNA Microarray V19.0 which contained 2006 miRNAs. We tested for significant differences in miRNA expression between paired carcinoma/adenoma/normal colonic tissue samples. Fewer than 600 miRNAs were expressed in >80% of people for colonic tissue; of these 86.5% were statistically differentially expressed between carcinoma and normal colonic mucosa using a false discovery rate of 0.05. Roughly half of these differentially expressed miRNAs showed a progression in levels of expression from normal to adenoma to carcinoma tissue. Other miRNAs appeared to be altered at the normal to adenoma stage, while others were only altered at the adenoma to carcinoma stage or only at the normal to carcinoma stage. Evaluation of the Agilent platform showed a high degree of repeatability (r = 0.98) and reasonable agreement with the NanoString platform. Our data suggest that miRNAs are highly dysregulated in colorectal tissue among individuals with colorectal cancer; the pattern of disruption varies by miRNA as tissue progresses from normal to adenoma to carcinoma.