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基于生物信息学探寻溃疡性结肠炎向结肠癌转变的关键基因及功能通路

Search for Key Genes and Functional Pathways of Ulcerative Colitis to Colon Cancer Based on Bioinformatics.

作者信息

Wang Shengbao, Zhen Lingling, Li Xiaoli, Fu Xu, Li Peiwu, Zhang Dekui

机构信息

Emergency Center, Gansu Emergency Medicine Clinical Research Center,Lanzhou University Second Hospital, Lanzhou, China.

Infectious Department, Lanzhou University Second Hospital, Lanzhou, China.

出版信息

Front Oncol. 2022 Mar 15;12:857148. doi: 10.3389/fonc.2022.857148. eCollection 2022.

Abstract

Ulcerative colitis (UC) is a persistent and diffuse inflammatory disease of the intestine. It is widely prevalent in developed countries. Approximately 30% of patients with UC suffer from widespread and aggressive colitis and are at increased risk of colon cancer. In this study, the genetic features and potential molecular mechanisms shared between UC and colorectal cancer were investigated. The datasets from GEO and TCGA were analyzed to obtain differentially expressed genes, of which there were 116 overlapping genes. A module containing 15 genes was obtained using String and Cytoscape to analyze the module and identify hub genes. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules associated with UC and colon cancer, with 52 overlapping genes. Functional clustering of the two gene cohorts was performed using the Metascape online tool, with three significant functions or pathways associated with both gene cohorts. A total of 19 key genes were included, and CCT2 was identified after expression and survival analyses. CCT2 is highly expressed in colon cancer and lowly expressed in UC, and its low expression is associated with a poor prognostic ratio. This study reveals, for the first time, that CCT2 may be a promoter of UC transformation into colon cancer and identifies new gene candidates that could be used as biomarkers or potential therapeutic targets.

摘要

溃疡性结肠炎(UC)是一种持续性且弥漫性的肠道炎症性疾病。它在发达国家广泛流行。大约30%的UC患者患有广泛且侵袭性的结肠炎,患结肠癌的风险增加。在本研究中,对UC和结直肠癌之间共享的遗传特征和潜在分子机制进行了研究。对来自GEO和TCGA的数据集进行分析以获得差异表达基因,其中有116个重叠基因。使用String和Cytoscape获得了一个包含15个基因的模块,以分析该模块并识别核心基因。使用加权基因共表达网络分析(WGCNA)来识别与UC和结肠癌相关的共表达模块,有52个重叠基因。使用Metascape在线工具对这两个基因群组进行功能聚类,有三个与这两个基因群组相关的显著功能或途径。总共纳入了19个关键基因,经表达和生存分析后鉴定出CCT2。CCT2在结肠癌中高表达,在UC中低表达,其低表达与不良预后率相关。本研究首次揭示,CCT2可能是UC转变为结肠癌的促进因子,并鉴定出可作为生物标志物或潜在治疗靶点的新基因候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffc/8965385/fd9be168f90d/fonc-12-857148-g001.jpg

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