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筛查肝硬化肝细胞癌患者非酒精性脂肪性肝病中异常甲基化和差异表达的基因。

Screening for aberrantly methylated and differentially expressed genes in nonalcoholic fatty liver disease of hepatocellular carcinoma patients with cirrhosis.

机构信息

Department of Gastroenterology, The Second People's Hospital of Liaocheng, No. 306, Health Street, Linqing, 252600, Shandong, China.

出版信息

World J Surg Oncol. 2022 Nov 18;20(1):364. doi: 10.1186/s12957-022-02828-3.

Abstract

BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) as the leading chronic liver disease worldwide causes hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to find potential aberrantly methylated and differentially expressed genes in NAFLD of HCC patients with cirrhosis.

METHODS

DNA methylation data, mRNA expression data, and the corresponding clinical information of HCC were downloaded from the Cancer Genome Atlas (TCGA, tissue sample) database. HCC patients with cirrhosis were divided into two groups according to the presence of NAFLD. The differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were obtained.

RESULTS

By overlapping 79 up-regulated genes and 1020 hypomethylated genes, we obtained 5 hypomethylated-highly expressed genes (Hypo-HGs). By overlapping 365 down-regulated genes and 481 hypermethylated genes, we identified 13 hypermethylated-lowly expressed genes (Hyper-LGs). Survival analysis of these 18 MDEGs indicated that the expression of DGKK and HOXD9 was significantly correlated with the overall survival time of NAFLD patients.

CONCLUSIONS

We identified several candidate genes whose expressions were regulated by DNA methylation of NAFLD of HCC with cirrhosis, which may provide a new field in understanding the clinical pathological mechanism of NAFLD of HCC with cirrhosis.

摘要

背景

非酒精性脂肪性肝病(NAFLD)作为全球主要的慢性肝病,可导致肝纤维化、肝硬化和肝细胞癌(HCC)。本研究旨在寻找肝硬化合并 NAFLD 的 HCC 患者中潜在的异常甲基化和差异表达基因。

方法

从癌症基因组图谱(TCGA,组织样本)数据库中下载 HCC 的 DNA 甲基化数据、mRNA 表达数据和相应的临床信息。根据是否存在 NAFLD 将 HCC 合并肝硬化的患者分为两组。获得差异表达基因(DEGs)和差异甲基化基因(DMGs)。

结果

通过重叠 79 个上调基因和 1020 个低甲基化基因,我们获得了 5 个低甲基化高表达基因(Hypo-HGs)。通过重叠 365 个下调基因和 481 个高甲基化基因,我们鉴定出 13 个高甲基化低表达基因(Hyper-LGs)。这些 18 个 MDEGs 的生存分析表明,DGKK 和 HOXD9 的表达与 NAFLD 患者的总生存时间显著相关。

结论

我们鉴定了一些候选基因,其表达受肝硬化合并 HCC 的 NAFLD 的 DNA 甲基化调控,这可能为理解肝硬化合并 HCC 的 NAFLD 的临床病理机制提供一个新的领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d035/9673405/ccb7b66d6211/12957_2022_2828_Fig1_HTML.jpg

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