摘要
目的:通过生物信息学技术探讨肾癌转移瘤细胞与原发性肾癌细胞基因表达差异,寻找关键的差异基因及与其可能相关的分子机制。方法:从GEO基因芯片数据库中下载人肾癌转移瘤和原发性肾癌的相关基因芯片数据GSE85258,用GCBI在线工具分析肾癌转移瘤和原发性肾癌的差异表达基因。分析差异表达基因GO及Pathway;筛选出既符合GO又符合Pathway的差异基因;将差异基因之间的相互作用及共表达关系构建基因网络图;构建差异基因Pathway网络图。通过体外细胞侵袭实验验证差异基因在肾癌细胞中的功能。结果:GSE85258数据集中共筛选出3000个差异基因,其中表面活性蛋白2(SFTPA2)升高最显著,SLC17A3降低最明显。GO分析显示,差异基因主要参与DNA依赖性转录,信号转导,小分子代谢过程等多个生物学功能。Pathway分析显示,差异基因主要参与内质网蛋白质加工,代谢途径,癌症途径等生物学过程。差异基因相互作用分析显示MAPK1为核心信号传递中介,PRKCA、NRAS、NOS1等基因与其直接作用。差异基因间共表达既有正相关也有负相关,其中与周围基因关系最多的10个基因,互为正相关。Pathway网络分析显示MAPK信号通路是上下游通路最多的信号通路,其包含细胞周期、细胞凋亡、P53信号通路、癌症途径等与肿瘤发生相关的信号通路。侵袭实验显示,抑制SFTPA2表达可降低肾癌细胞的侵袭能力(t=18.44,P<0.01)。结论:肾癌转移瘤细胞与原发性肾癌细胞存在表达差异基因,其中SFTPA2、MAPK1、PRKCA、NOS1可能是关键差异基因,其可能参与MAPK信号通路等,促进肾癌转移。
Objective:To explore the difference in gene expression between renal cancer metastatic tumor cells and primary renal cancer cells by bioinformatics technology,and to find the key differential genes and the potential molecular mechanism.Methods:The gene chip data GSE85258 of human renal cancer metastases and primary renal cancer was downloaded from the GEO gene chip database,and the differentially expressed genes of renal cancer metastases and primary renal cancer were analyzed using the GCBI online tool.By analyzing the differentially expressed genes GO and Pathway,the differential genes that meet both GO and Pathway were screened out;and then we constructed a gene network map of the interactions and co-expression relationships between the differential genes;and constructed a pathway network map of the differential genes.The function of differential genes in renal cancer cells was verified by in vitro cell invasion experiments.Results:A total of 3000 differential genes were screened in the GSE85258 data set,of which SFTPA2 increased significantly and SLC17A3 decreased markedly.GO analysis found that these differential genes mainly focused on multiple biological functions,such as DNA-dependent transcription,signal transduction,and small molecule metabolic processes.Pathway analysis showed that these differential genes are mainly involved in biological processes,such as endoplasmic reticulum protein processing,metabolic pathways,and cancer-related pathways.Analysis of differential gene interactions revealed that MAPK1 is the core signalling intermediary,and PRKCA,NRAS,and NOS1 genes directly interact with MAPK1.The co-expression analysis of differential genes showed that there were positive and negative correlations between the co-expressions of the differential genes.Among them,the 10 genes most closely related to the surrounding genes were positively correlated with each other.Pathway network analysis shows that the MAPK signal pathway is the most upstream and downstream pathway,including cell cycle,apoptosis,P53
作者
张金虎
周洋
王诚悦
邹元章
汪浩洋
卢俅
孙浩
ZHANG Jin-hu;ZHOU Yang;WANG Cheng-yue;ZOU Yuan-zhang;WANG Hao-yang;LU Qiu;SUN Hao(Department of Urology, Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212013,China)
出处
《江苏大学学报（医学版）》
CAS
2020年第1期39-44,共6页
Journal of Jiangsu University：Medicine Edition
关键词
生物信息学
肾癌转移瘤
原发性肾癌
基因网络
bioinformatics
renal cancer metastases
primary renal cancer
gene network
