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胃癌中长非编码 RNA 表达谱分析。

Analysis of long non-coding RNA expression profiles in gastric cancer.

机构信息

Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2013 Jun 21;19(23):3658-64. doi: 10.3748/wjg.v19.i23.3658.

Abstract

AIM

To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer.

METHODS

Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P-values below 0.01 were considered differentially expressed. An independent data set was used to validate the results.

RESULTS

With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P-value < 0.01) with the same direction.

CONCLUSION

We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.

摘要

目的

研究长链非编码 RNA(lncRNA)在胃癌中的表达模式。

方法

从基因表达综合数据库(GEO)下载了两个公开的人类胃癌外显子芯片和相应的正常组织数据。我们重新注释了人类外显子芯片的探针,并保留了在基因水平上唯一映射到 lncRNA 的探针。使用 affymetrix power tools 中的稳健多阵列平均方法生成 lncRNA 表达谱。然后使用 Bioconductor 包线性模型进行微阵列数据分析,将调整后的 P 值低于 0.01 的基因视为差异表达基因。使用独立数据集验证结果。

结果

通过建立一个计算流程来重新注释 Affymetrix Human Exon 1.0 ST 芯片的超过 650 万个探针,我们鉴定了 136053 个在基因水平上唯一映射到 lncRNA 的探针。这些探针对应于 9294 个 lncRNA,覆盖了近 76%的 GENCODE lncRNA 数据集。通过分析包含 80 对胃癌和正常相邻组织样本的 GSE27342 数据集,我们鉴定了 88 个在胃癌中差异表达的 lncRNA,其中一些已被报道在癌症中发挥作用,如 LINC00152、牛磺酸上调 1、尿路上皮癌相关 1、Pvt1 癌基因、小核仁 RNA 宿主基因 1 和 LINC00261。在验证数据集 GSE33335 中,这些差异表达的 lncRNA 中有 59%(调整后的 P 值<0.01)表现出相同方向的显著表达变化。

结论

我们鉴定了一组在胃癌中差异表达的 lncRNA,为发现胃癌的新生物标志物和治疗靶点提供了有用的信息。

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