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食管腺癌中基因表达特征的表观遗传调控

Epigenetic regulation on the gene expression signature in esophagus adenocarcinoma.

作者信息

Xi Ting, Zhang Guizhi

机构信息

Department of Gastroenterology, People's Hospital of Liaocheng of Shandong Province, China.

Department of Gastroenterology, Second People's Hospital of Liaocheng of Shandong Province, China.

出版信息

Pathol Res Pract. 2017 Feb;213(2):83-88. doi: 10.1016/j.prp.2016.12.007. Epub 2016 Dec 19.

Abstract

BACKGROUND

Understanding the molecular mechanisms represents an important step in the development of diagnostic and therapeutic measures of esophagus adenocarcinoma (NOS). The objective of this study is to identify the epigenetic regulation on gene expression in NOS, shedding light on the molecular mechanisms of NOS.

METHODS

In this study, 78 patients with NOS were included and the data of mRNA, miRNA and DNA methylation of were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis between NOS and controls was performed in terms of gene expression, miRNA expression, and DNA methylation. Bioinformatic analysis was followed to explore the regulation mechanisms of miRNA and DNA methylationon gene expression.

RESULTS

Totally, up to 1320 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs were identified. 240 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. 101 DEGs were found to be highlymethylated in CpG islands. Then, 8 differentially methylated genes (DMGs) were selected, which showed down-regulated expression in NOS. Among of these genes, 6 genes including ADHFE1, DPP6, GRIA4, CNKSR2, RPS6KA6 and ZNF135 were target genes of differentially expressed miRNAs (hsa-mir-335, hsa-mir-18a, hsa-mir-93, hsa-mir-106b and hsa-mir-21).

CONCLUSIONS

The identified altered miRNA, genes and DNA methylation site may be applied as biomarkers for diagnosis and prognosis of NOS.

摘要

背景

了解分子机制是食管腺癌(NOS)诊断和治疗措施发展中的重要一步。本研究的目的是确定NOS中基因表达的表观遗传调控,以阐明NOS的分子机制。

方法

本研究纳入了78例NOS患者,并从癌症基因组图谱(TCGA)下载了mRNA、miRNA和DNA甲基化数据。对NOS组和对照组进行基因表达、miRNA表达和DNA甲基化的差异分析。随后进行生物信息学分析,以探索miRNA和DNA甲基化对基因表达的调控机制。

结果

共鉴定出1320个差异表达基因(DEG)和32个差异表达miRNA。240个DEG不仅是靶基因,而且与筛选出的差异表达miRNA呈负相关。发现101个DEG在CpG岛中高度甲基化。然后,选择了8个差异甲基化基因(DMG),它们在NOS中表达下调。在这些基因中,包括ADHFE1、DPP6、GRIA4、CNKSR2、RPS6KA6和ZNF135在内的6个基因是差异表达miRNA(hsa-mir-335、hsa-mir-18a、hsa-mir-93、hsa-mir-106b和hsa-mir-21)的靶基因。

结论

所鉴定出的改变的miRNA、基因和DNA甲基化位点可作为NOS诊断和预后的生物标志物。

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