结直肠癌中O-型糖基化相关差异基因的筛选及分析

doi:10.3969/j.issn.1006-7795.2020.03.016

摘要/Abstract

摘要： 目的通过鉴定得出正常和异常O-型糖基化结肠癌细胞之间的差异表达基因（differentially expressed genes，DEGs），即O-型糖基化相关差异基因，并探讨其促进肿瘤发生发展的潜在机制。方法运用单色标记表达谱芯片技术对经Cosmc表达质粒或其空白对照质粒稳定转染的LS174T Tn（+）细胞进行检测，采用RNA杂交获得基因表达谱数据，通过Wegstalt平台的基因通路富集（gene set enrichment analysis，GESA）方法行GO基因本体（gene ontology，GO）分析和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）肿瘤相关通路分析，R语言行热图聚类分析，STRING在线软件对蛋白网络进行差异及整合分析。结果通过分析获得了1 474个符合条件的DEGs，其中有502个基因上调，972个基因下调；GO分析显示DEGs主要参与细胞外基质组织及生长因子活性相关的生物学过程；KEGG分析DEGs主要富集在磷脂酰肌醇-3激酶（phosphatidylinositol 3-kinase，PI3K）、转化生长因子-β（transforming growth factor-β，TGF-β）和Wnt等经典信号通路上。结论本研究首次着眼于结肠癌细胞中由O-型糖基化引起的转录组学变化，有助于揭示O-型糖基化修饰的结直肠癌分子特征，并为科学研究和临床治疗提供新的方向。

关键词: 结直肠癌, O-型糖基化, 基因表达谱, 差异表达基因, Cosmc, 生物信息学

Abstract: Objective To identify differentially expressed genes (DEGs) between normal and abnormal O-glycosylated colon cancer cells, which are regarded as directly O-glycosylation-associated genes, and to investigate their underlying mechanisms. Methods The gene expression profiles of LS174T Tn (+) cells stably transfected with Cosmc or control plasmid were subjected to one-color microarray-based gene expression profiles. After RNA hybridization, gene expression profiles were obtained, and differential and integrative analysis was performed on Wegstalt platform by gene set enrichment analysis (GESA). Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) tumor-related pathways analysis, R software packages, and protein-protein interaction (PPI) networks by STRING were conducted. Results A total of 1474 genes, including 502 up-regulated genes and 972 down-regulated genes, were selected as DEGs. GO analysis demonstrates that both up-regulated and down-regulated DEGs are enriched for numerous biological processes such as extracellular matrix organization and growth factor activity. DEGs are mainly enriched in several tumor-associated pathways such as phosphatidylinositol 3-kinase (PI3K) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway, and Wnt signaling pathway. Conclusion This study is the first work focused on the transcriptional changes caused by O-glycosylation in colon cancer cells, which helps to uncover the molecular characteristics of O-glycosylated colorectal cancer(CRC) cells and may provide new targets for future research and therapy.

Key words: colorectal cancer, O-glycosylation, gene expression profile, differentially expressed genes, Cosmc, bioinformatics

中图分类号:

R735.3

姚健楠, 高天博, 段凌, 刘健, 蒋玉良, 安广宇, 葛洋. 结直肠癌中O-型糖基化相关差异基因的筛选及分析[J]. 首都医科大学学报, 2020, 41(3): 403-410.

Yao Jiannan, Gao Tianbo, Duan Ling, Liu Jian, Jiang Yuliang, An Guangyu, Ge Yang. Screening and analysis of O-glycosylation-associated differential expressed genes in colorectal cancer[J]. Journal of Capital Medical University, 2020, 41(3): 403-410.

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