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女性肥胖与结肠癌之间可能存在遗传关联。

A possible genetic association between obesity and colon cancer in females.

机构信息

Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Department of Hepatobiliary Transplantation, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

出版信息

Front Endocrinol (Lausanne). 2023 Aug 30;14:1189570. doi: 10.3389/fendo.2023.1189570. eCollection 2023.

Abstract

OBJECT

There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms.

METHODS

GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions.

RESULTS

Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p.

CONCLUSION

Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.

摘要

目的

越来越多的临床证据表明,肥胖症的增加与癌症发病率和死亡率的增加有关。虽然研究表明肥胖与结肠癌之间存在关联,但肥胖与女性结肠癌之间相互作用的特定机制尚不清楚。本研究旨在利用生物信息学阐明女性肥胖与结肠癌之间的遗传联系,并探讨可能的分子机制。

方法

从基因表达综合数据库(GEO)中获取 GSE44076 和 GSE199063 微阵列数据集。在线工具 GEO2R 用于在两个微阵列数据集和健康对照组中研究肥胖症和结肠癌之间的差异基因。合并两个研究中鉴定的差异基因(DEGs)。对 DEGs 进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。然后使用 STRING 数据库和 Cytoscape 软件构建蛋白质-蛋白质相互作用(PPI)网络以发现枢纽基因。还使用 NetworkAnalyst 构建靶标 microRNAs(miRNAs)和枢纽基因网络以及转录物网络。

结果

在两个数据集之间,有 146 个 DEGs 是共享的。GO 分析和 KEGG 通路富集分析表明,DEGs 主要富集在炎症和免疫相关通路中。使用 Cytoscape 软件的 MCODE 和 CytoNCA 插件构建 PPI 网络,鉴定出 14 个枢纽基因:TYROBP、CD44、BGN、FCGR3A、CD53、CXCR4、FN1、SPP1、IGF1、CCND1、MMP9、IL2RG、IL6 和 CTGF。这些枢纽基因的关键转录因子包括 WRNIP1、ATF1、CBFB 和 NR2F6。这些枢纽基因的关键 miRNAs 包括 hsa-mir-1-3p、hsa-mir-26b-5p、hsa-mir-164a-5p 和 hsa-mir-9-5p。

结论

本研究表明,患有结肠癌和肥胖症的女性患者存在共同改变的基因。这些基因通过与炎症和免疫系统相关的途径,在这两种疾病的发生中发挥重要作用。我们构建了枢纽基因与靶向转录因子的 miRNAs 之间的网络,这可能为该领域的进一步研究提供思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a26/10497871/9d8abb0e1443/fendo-14-1189570-g001.jpg

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