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基于基因表达综合数据库和 DNA 甲基化分析揭示结直肠癌中的潜在基因。

Uncovering potential genes in colorectal cancer based on integrated and DNA methylation analysis in the gene expression omnibus database.

机构信息

The Second Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Institute of Tumor, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

BMC Cancer. 2022 Feb 3;22(1):138. doi: 10.1186/s12885-022-09185-0.

DOI:10.1186/s12885-022-09185-0
PMID:35114976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8815138/
Abstract

BACKGROUND

Colorectal cancer (CRC) is major cancer-related death. The aim of this study was to identify differentially expressed and differentially methylated genes, contributing to explore the molecular mechanism of CRC.

METHODS

Firstly, the data of gene transcriptome and genome-wide DNA methylation expression were downloaded from the Gene Expression Omnibus database. Secondly, functional analysis of differentially expressed and differentially methylated genes was performed, followed by protein-protein interaction (PPI) analysis. Thirdly, the Cancer Genome Atlas (TCGA) dataset and in vitro experiment was used to validate the expression of selected differentially expressed and differentially methylated genes. Finally, diagnosis and prognosis analysis of selected differentially expressed and differentially methylated genes was performed.

RESULTS

Up to 1958 differentially expressed (1025 up-regulated and 993 down-regulated) genes and 858 differentially methylated (800 hypermethylated and 58 hypomethylated) genes were identified. Interestingly, some genes, such as GFRA2 and MDFI, were differentially expressed-methylated genes. Purine metabolism (involved IMPDH1), cell adhesion molecules and PI3K-Akt signaling pathway were significantly enriched signaling pathways. GFRA2, FOXQ1, CDH3, CLDN1, SCGN, BEST4, CXCL12, CA7, SHMT2, TRIP13, MDFI and IMPDH1 had a diagnostic value for CRC. In addition, BEST4, SHMT2 and TRIP13 were significantly associated with patients' survival.

CONCLUSIONS

The identified altered genes may be involved in tumorigenesis of CRC. In addition, BEST4, SHMT2 and TRIP13 may be considered as diagnosis and prognostic biomarkers for CRC patients.

摘要

背景

结直肠癌（CRC）是主要的癌症相关死亡原因。本研究旨在鉴定差异表达和差异甲基化基因，以探索 CRC 的分子机制。

方法

首先，从基因表达综合数据库下载基因转录组和全基因组 DNA 甲基化表达数据。其次，对差异表达和差异甲基化基因进行功能分析，然后进行蛋白质-蛋白质相互作用（PPI）分析。第三，使用癌症基因组图谱（TCGA）数据集和体外实验验证选定的差异表达和差异甲基化基因的表达。最后，对选定的差异表达和差异甲基化基因进行诊断和预后分析。

结果

共鉴定出 1958 个差异表达（1025 个上调和 993 个下调）基因和 858 个差异甲基化（800 个高甲基化和 58 个低甲基化）基因。有趣的是，一些基因，如 GFRA2 和 MDFI，是差异表达-甲基化基因。嘌呤代谢（涉及 IMPDH1）、细胞黏附分子和 PI3K-Akt 信号通路是显著富集的信号通路。GFRA2、FOXQ1、CDH3、CLDN1、SCGN、BEST4、CXCL12、CA7、SHMT2、TRIP13、MDFI 和 IMPDH1 对 CRC 具有诊断价值。此外，BEST4、SHMT2 和 TRIP13 与患者的生存显著相关。

结论

鉴定出的改变基因可能参与 CRC 的肿瘤发生。此外，BEST4、SHMT2 和 TRIP13 可作为 CRC 患者的诊断和预后生物标志物。

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