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通过综合生物信息学分析鉴定 MEDAG 作为 2 型糖尿病发病和进展的枢纽候选基因。

Identification of MEDAG as a Hub Candidate Gene in the Onset and Progression of Type 2 Diabetes Mellitus by Comprehensive Bioinformatics Analysis.

机构信息

Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China.

Department of Endocrinology, The Third People's Hospital of Hangzhou, Hangzhou 310009, China.

出版信息

Biomed Res Int. 2021 Feb 25;2021:3947350. doi: 10.1155/2021/3947350. eCollection 2021.

DOI:10.1155/2021/3947350
PMID:33728329
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7938259/
Abstract

OBJECTIVES

We conducted the present study to identify novel hub candidate genes in the pathogenesis of type 2 diabetes mellitus (T2DM) and provide potential biomarkers or therapeutic targets for dealing with the disease.

METHODS

We conducted weighted gene coexpression network analysis on a series of the expression profiles of the pancreas islet of T2DM patients obtained from the Gene Expression Omnibus database to construct a weighted coexpression network. After dividing genes into separated coexpression modules, we identified a T2DM-related module using Pearson's correlation analysis. Then, hub genes were identified from the T2DM-related module using the Maximal Clique Centrality method and validated by correlation analysis with clinical traits, differentially expressed gene analysis, validation in other datasets, and single-gene gene set enrichment analysis (GSEA).

RESULTS

Genes were divided into 16 coexpression modules, and one module was identified as a T2DM-related module. Four hub candidate genes were identified, and MEDAG was a novel hub candidate gene. The expression level of MEDAG was positively correlated with hemoglobin A1c (HbA1c) and was evidently overexpressed in the pancreas islet tissue of T2DM patients compared with normal control. Analyses on two other datasets supported the results. GSEA verified that MEDAG plays essential roles in T2DM.

CONCLUSIONS

MEDAG is a novel hub candidate of T2DM, and its irregular expression in the pancreas islet plays vital roles in the pathogenesis of T2DM. MEDAG is a potential target of intervention in the future for the treatment of T2DM.

摘要

目的

本研究旨在鉴定 2 型糖尿病（T2DM）发病机制中的新型枢纽候选基因，并为该疾病的治疗提供潜在的生物标志物或治疗靶点。

方法

我们对来自基因表达综合数据库的 T2DM 患者胰岛表达谱进行了加权基因共表达网络分析，构建了加权共表达网络。将基因分为独立的共表达模块后，我们通过 Pearson 相关分析鉴定了一个与 T2DM 相关的模块。然后，我们使用最大团中心度法从 T2DM 相关模块中鉴定出枢纽候选基因，并通过与临床特征、差异表达基因分析、其他数据集验证以及单基因基因集富集分析（GSEA）进行相关性分析进行验证。

结果

基因被分为 16 个共表达模块，其中一个模块被鉴定为与 T2DM 相关的模块。鉴定出 4 个枢纽候选基因，其中 MEDAG 是一个新的枢纽候选基因。MEDAG 的表达水平与糖化血红蛋白（HbA1c）呈正相关，并且在 T2DM 患者的胰岛组织中明显过表达，与正常对照相比。对另外两个数据集的分析支持了这一结果。GSEA 验证了 MEDAG 在 T2DM 中发挥重要作用。

结论

MEDAG 是 T2DM 的一个新型枢纽候选基因，其在胰岛中的异常表达在 T2DM 的发病机制中起着重要作用。MEDAG 是未来治疗 T2DM 的潜在干预靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/c12728cdf49a/BMRI2021-3947350.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/95742fbac72c/BMRI2021-3947350.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/ccd63939b67a/BMRI2021-3947350.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/24b0889787c8/BMRI2021-3947350.007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/c12728cdf49a/BMRI2021-3947350.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/95742fbac72c/BMRI2021-3947350.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/8b5ac3864309/BMRI2021-3947350.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/958534e6a4b8/BMRI2021-3947350.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/ffdd9d474512/BMRI2021-3947350.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/477926c53b78/BMRI2021-3947350.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/ccd63939b67a/BMRI2021-3947350.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/24b0889787c8/BMRI2021-3947350.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/15dd39524842/BMRI2021-3947350.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f3d/7938259/c12728cdf49a/BMRI2021-3947350.009.jpg

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