Integrative genomics analysis of genes with biallelic loss and its relation to the expression of mRNA and micro-RNA in esophageal squamous cell carcinoma.
Integrative genomics analysis of genes with biallelic loss and its relation to the expression of mRNA and micro-RNA in esophageal squamous cell carcinoma.
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DOI：
10.1186/s12864-015-1919-0
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发表时间：
2015-09-26
期刊：
影响因子：
4.4
通讯作者：
Taylor PR
中科院分区：
文献类型：
--
作者：
Hu N;Wang C;Clifford RJ;Yang HH;Su H;Wang L;Wang Y;Xu Y;Tang ZZ;Ding T;Zhang T;Goldstein AM;Giffen C;Lee MP;Taylor PR
基因组不稳定性在人类癌症中起着重要作用。我们之前在肿瘤的杂合性缺失（LOH）和拷贝数（CN）变化方面描述了食管鳞状细胞癌（ESCC）的基因组不稳定性。在目前的研究中，我们利用来自中国一个高风险地区的30例ESCC患者的500K SNP、mRNA和miRNA阵列的结果，重点研究ESCC中双等位基因丢失及其与mRNA和miRNA表达的关系。双等位基因丢失并不常见，但当它发生时，它表现出一致的模式：在至少10%的ESCC样本中，只有77个基因（< 0.5%）显示双等位基因丢失，但几乎所有这些基因都集中在四个染色体臂上（即3p上的42个基因，9p上的14个基因，5q上的10个基因，4p上的7个基因）。（ii）双等位基因丢失与较低的mRNA表达相关：77个基因中有52个也有RNA表达数据，41个（79%）双等位基因丢失病例的表达水平低于没有双等位基因丢失的病例。（iii）双等位基因缺失与miRNA表达的关系不太清楚，但似乎倾向于更高的miRNA水平：在60对miRNA靶基因对中，34对（57%）双等位基因缺失的miRNA表达高于未缺失的miRNA表达，而26对（43%）miRNA表达较低。（iv）最后，双等位基因丢失对miRNA和mRNA表达关系的影响是复杂的。双等位基因缺失最常与miRNA升高和mRNA减少的模式相关（43%），但miRNA和mRNA同时减少的模式也很常见（35%）。我们的研究结果表明，双等位基因丢失在ESCC中并不常见，但当它发生时，它定位于几个特定的染色体区域，并与受影响基因的mRNA表达减少有关。双等位基因缺失对miRNA表达的影响以及miRNA与mRNA表达之间的关系是复杂的。本文的在线版本（doi:10.1186/s12864-015-1919-0）包含补充材料，可供授权用户使用。
Genomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) and copy number (CN) changes in tumors. In the current study we focus on biallelic loss and its relation to expression of mRNA and miRNA in ESCC using results from 500K SNP, mRNA, and miRNA arrays in 30 cases from a high-risk region of China. (i) Biallelic loss was uncommon but when it occurred it exhibited a consistent pattern: only 77 genes (<0.5 %) showed biallelic loss in at least 10 % of ESCC samples, but nearly all of these genes were concentrated on just four chromosomal arms (ie, 42 genes on 3p, 14 genes on 9p, 10 genes on 5q, and seven genes on 4p). (ii) Biallelic loss was associated with lower mRNA expression: 52 of the 77 genes also had RNA expression data, and 41 (79 %) showed lower expression levels in cases with biallelic loss compared to those without. (iii) The relation of biallelic loss to miRNA expression was less clear but appeared to favor higher miRNA levels: of 60 miRNA-target gene pairs, 34 pairs (57 %) had higher miRNA expression with biallelic loss than without, while 26 pairs (43 %) had lower miRNA expression. (iv) Finally, the effect of biallelic loss on the relation between miRNA and mRNA expression was complex. Biallelic loss was most commonly associated with a pattern of elevated miRNA and reduced mRNA (43 %), but a pattern of both reduced miRNA and mRNA was also common (35 %). Our results indicate that biallelic loss in ESCC is uncommon, but when it occurs it is localized to a few specific chromosome regions and is associated with reduced mRNA expression of affected genes. The effect of biallelic loss on miRNA expression and on the relation between miRNA and mRNA expressions was complex. The online version of this article (doi:10.1186/s12864-015-1919-0) contains supplementary material, which is available to authorized users.