Yun Zhang-Jun, Wang Hui-Jing, Yu Yi-Xuan, Sun Zi-Yi, Yao Shu-Kun
Beijing University of Chinese Medicine Beijing 100029,China.
Department of Gastroenterology,China-Japan Friendship Hospital Beijing 100029,China.
Zhongguo Zhong Yao Za Zhi. 2022 Mar;47(6):1666-1676. doi: 10.19540/j.cnki.cjcmm.20211108.402.
This study screened and analyzed the differentially expressed genes(DEGs) between colorectal cancer(CRC) tissues and normal tissues with bioinformatics techniques to predict biomarkers and Chinese medicinals for the diagnosis and treatment of CRC. The microarray data sets GSE21815, GSE106582, and GSE41657 were downloaded from the Gene Expression Omnibus(GEO), and the DEGs were screened by GEO2 R, followed by the Gene Ontology(GO) tern enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the DEGs based on DAVID. The protein-protein interaction network was constructed by STRING, and MCODE and Cytohubba plug-ins were used to screen the significant modules and hub genes in the network. UCSC, cBioPortal, and Oncomine were employed for hierarchical clustering, survival analysis, Oncomine analysis, and correlation analysis of clinical data. Coremine Medical was applied to predict the Chinese medicinals acting on hub genes. A total of 284 DEGs were screened out, with 146 up-regulated and 138 down-regulated. The up-regulated genes were mainly involved in cell cycle, NLRs pathway, and TNF signaling pathway, and the down-regulated genes were related to mineral absorption, nitrogen metabolism, and bicarbonate reabsorption in proximal tubules. The 15 hub genes were CDK1, CDC20, AURKA, MELK, TOP2 A, PTTG1, BUB1, CDCA5, CDC45, TPX2, NEK2, CEP55, CENPN, TRIP13, and GINS2, among which CDK1 and CDC20 were regarded as core genes. The high expression of CDK1 and CDC20 suggested poor prognosis, and they significantly expressed in many cancers, especially breast cancer, lung cancer, and CRC. The expression of CDK1 and CDC20 was correlated with gender, tumor type, TNM stage, and KRAS gene mutation. The potential effective medicinals against CRC were Scutellariae Radix, Scutellariae Barbatae Herba, Arnebiae Radix, etc. The significant expression of CDK1 and CDC20 can help distinguish tumor tissues from normal tissues, and is related to survival prognosis. Thus, the two can be used as biomarkers for the diagnosis and treatment of CRC. This study provides a reference for related drug development.
本研究运用生物信息学技术筛选并分析了结直肠癌（CRC）组织与正常组织之间的差异表达基因（DEGs），以预测用于CRC诊断和治疗的生物标志物及中药。从基因表达综合数据库（GEO）下载了微阵列数据集GSE21815、GSE106582和GSE41657，并通过GEO2R筛选DEGs，随后基于DAVID对DEGs进行基因本体论（GO）术语富集和京都基因与基因组百科全书（KEGG）通路富集分析。利用STRING构建蛋白质-蛋白质相互作用网络，并使用MCODE和Cytohubba插件筛选网络中的显著模块和枢纽基因。运用UCSC、cBioPortal和Oncomine进行层次聚类、生存分析、Oncomine分析以及临床数据的相关性分析。应用Coremine Medical预测作用于枢纽基因的中药。共筛选出284个DEGs，其中146个上调，138个下调。上调基因主要参与细胞周期、NLRs通路和TNF信号通路，下调基因与矿物质吸收、氮代谢以及近端小管中的碳酸氢盐重吸收有关。15个枢纽基因为CDK1、CDC20、AURKA、MELK、TOP2A、PTTG1、BUB1、CDCA5、CDC45、TPX2、NEK2、CEP55、CENPN、TRIP13和GINS2，其中CDK1和CDC20被视为核心基因。CDK1和CDC20的高表达提示预后不良，且它们在多种癌症中显著表达，尤其是乳腺癌、肺癌和CRC。CDK1和CDC20的表达与性别、肿瘤类型、TNM分期以及KRAS基因突变相关。针对CRC的潜在有效药物有黄芩、半枝莲、紫草等。CDK1和CDC20的显著表达有助于区分肿瘤组织与正常组织，且与生存预后相关。因此，二者可作为CRC诊断和治疗的生物标志物。本研究为相关药物研发提供了参考。
