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通过综合生物信息学分析筛选结直肠癌的关键基因和信号通路。

Screening key genes and signaling pathways in colorectal cancer by integrated bioinformatics analysis.

机构信息

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Mol Med Rep. 2019 Aug;20(2):1259-1269. doi: 10.3892/mmr.2019.10336. Epub 2019 Jun 4.

Abstract

The aim of the present study was to identify potential key genes associated with the progression and prognosis of colorectal cancer (CRC). Differentially expressed genes (DEGs) between CRC and normal samples were screened by integrated analysis of gene expression profile datasets, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to identify the biological role of DEGs. In addition, a protein‑protein interaction network and survival analysis were used to identify the key genes. The profiles of GSE9348, GSE22598 and GSE113513 were downloaded from the GEO database. A total of 405 common DEGs were identified, including 236 down‑ and 169 upregulated. GO analysis revealed that the downregulated DEGs were mainly enriched in 'detoxification of copper ion' [biological process, (BP)], 'oxidoreductase activity, acting on CH‑OH group of donors, NAD or NADP as acceptor' [molecular function, (MF)] and 'brush border' [cellular component, (CC)]. Upregulated DEGs were mainly involved in 'nuclear division' (BP), 'snoRNA binding' (MF) and 'nucleolar part' (CC). KEGG pathway analysis revealed that DEGs were mainly involved in 'mineral absorption', 'nitrogen metabolism', 'cell cycle' and 'caffeine metabolism'. A PPI network was constructed with 268 nodes and 1,027 edges. The top one module was selected, and it was revealed that module‑related genes were mainly enriched in the GO terms 'sister chromatid segregation' (BP), 'chemokine activity' (MF), and 'condensed chromosome (CC)'. The KEGG pathway was mainly enriched in 'cell cycle', 'progesterone‑mediated oocyte maturation', 'chemokine signaling pathway', 'IL‑17 signaling pathway', 'legionellosis', and 'rheumatoid arthritis'. DNA topoisomerase II‑α (TOP2A), mitotic arrest deficient 2 like 1 (MAD2L1), cyclin B1 (CCNB1), checkpoint kinase 1 (CHEK1), cell division cycle 6 (CDC6) and ubiquitin conjugating enzyme E2 C (UBE2C) were indicated as hub genes. Furthermore, survival analysis revealed that TOP2A, MAD2L1, CDC6 and CHEK1 may serve as prognostic biomarkers in CRC. The present study provided insights into the molecular mechanism of CRC that may be useful in further investigations.

摘要

本研究旨在鉴定与结直肠癌(CRC)进展和预后相关的潜在关键基因。通过整合基因表达谱数据集,包括基因表达综合数据库(GEO)和癌症基因组图谱(TCGA),筛选 CRC 和正常样本之间的差异表达基因(DEGs)。进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析,以鉴定 DEGs 的生物学作用。此外,还进行了蛋白质-蛋白质相互作用网络和生存分析,以鉴定关键基因。从 GEO 数据库中下载了 GSE9348、GSE22598 和 GSE113513 的图谱。共鉴定出 405 个共同的 DEGs,包括 236 个下调和 169 个上调。GO 分析显示,下调的 DEGs 主要富集在“铜离子解毒”[生物过程,(BP)]、“氧化还原酶活性,作用于供体 CH-OH 基团,NAD 或 NADP 作为受体”[分子功能,(MF)]和“刷状缘”[细胞成分,(CC)]。上调的 DEGs 主要参与“核分裂”(BP)、“snoRNA 结合”(MF)和“核仁部分”(CC)。KEGG 通路分析显示,DEGs 主要参与“矿物质吸收”、“氮代谢”、“细胞周期”和“咖啡因代谢”。构建了一个包含 268 个节点和 1027 条边的 PPI 网络。选择了一个顶部模块,结果表明模块相关基因主要富集在 GO 术语“姐妹染色单体分离”(BP)、“趋化因子活性”(MF)和“浓缩染色体”(CC)。KEGG 通路主要富集于“细胞周期”、“孕激素介导的卵母细胞成熟”、“趋化因子信号通路”、“IL-17 信号通路”、“军团菌病”和“类风湿性关节炎”。DNA 拓扑异构酶 II-α(TOP2A)、有丝分裂阻滞缺陷 2 样 1(MAD2L1)、细胞周期蛋白 B1(CCNB1)、检查点激酶 1(CHEK1)、细胞分裂周期 6(CDC6)和泛素结合酶 E2 C(UBE2C)被认为是枢纽基因。此外,生存分析表明 TOP2A、MAD2L1、CDC6 和 CHEK1 可能作为 CRC 的预后生物标志物。本研究为 CRC 的分子机制提供了新的见解,可能对进一步的研究有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e89/6625394/c7375c72fe46/MMR-20-02-1259-g00.jpg

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