摘要
目的获取Ras亚家族新分支的创始成员RIT1蛋白(GTP-binding protein Rit1,RIT1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达水平数据,分析RIT1及其共表达基因在HCC发生发展过程中的作用。方法通过Oncomine数据库和癌症基因图谱(the cancer genome atlas,TCGA)数据库分析RIT1基因在HCC中的表达,及临床特征和预后的关系。利用cBioportal在线分析工具分析RIT1在HCC中的突变情况,并通过GeneMina数据库分析与RIT1相互作用的蛋白。基于LinkedOmics数据库筛选与RIT1在HCC中共表达的蛋白并分析其参与的信号通路。结果HCC组织中RIT1 mRNA表达和DNA拷贝数变异(copy number variation,CNV)显著高于正常组织(P<0.01),HCC患者中肿瘤组织的RIT1转录水平显著高于正常组织;随着肿瘤等级和疾病阶段的升高,RIT1的表达量具有升高的趋势。在360例HCC样本中共有62例发生RIT1基因变异,变异率约为17.2%。生存曲线分析显示,RIT1高表达组和RIT1变异组的总体生存期短于RIT1低表达组和无变异组(P<0.01)。RAF原癌基因丝氨酸/苏氨酸蛋白激酶(RAF proto-oncogene serine/threonine-protein kinase,RAF)、神经营养的酪氨酸激酶1型受体(neurotrophic receptor tyrosine kinase 1,NTRK1)、Ral鸟嘌呤核苷酸解离刺激剂样蛋白1(Ral GDP dissociation stimulator like 1,RGL1)、神经生长因子(nerve growth factor,NGF)、RLF锌指蛋白、鸟嘌呤核苷酸解离刺激因子(Ral guanine nucleotide-dissociation stimulator,RalGDS)、干扰素相关发育调节因子1(interferon-related developmental regulator 1,IFRD1)、Ras相关蛋白1b(RAS-related protein Rap-1b,RAP1B)、Kelch样家族成员12(Kelch like family member 12,KLHL12)、MLLT4、母系DPP同源物3(mothers against decapentaplegic homolog 3,Smad3)等蛋白与RIT1具有明显的相互作用,STX6、MPZL1、PKM2、RNF24和SOAT1等蛋白在HCC中与RIT1共表达,这些蛋白主要涉及小G蛋白信号转导、Ras信号通路和神经营养因子TRK受体信号通路,能够促进DNA构象改变、有丝分裂和细胞周期等。结论RIT1在HCC组织中呈高表达,具有较高的基因变异频率,并且与患者预后不良相关,为之后深入研究RIT1在HCC发生发展中的作用提供了理论依据。
Objective To obtain the expression level of GTP-binding protein Rit1 (RIT1),a founding member of the new branch of Ras subfamily,in hepatocellular carcinoma (HCC).The role of RIT1 and its co-expressed genes in the development and progression of HCC was analyzed.Methods Firstly,the expression of RIT1 gene in HCC was analyzed by Oncomine database and the cancer genome atlas (TCGA) database,as well as the relationship between clinical features and prognosis.The cBioportal online analysis tool was used to analyze the mutation of RIT1 in HCC,and the RIT1 interacting proteins were analyzed by GeneMina database.Based on the LinkedOmics database,co-expression proteins of RIT1 in HCC were screened and their participating signaling pathways were analyzed.Results The mRNA expression and DNA copy number variation (CNV) of RIT1 in HCC tissues were significantly higher than those in normal tissues(P<0.01).The transcription level of RIT1 in tumor tissues in HCC patients was significantly higher than that in normal tissues.With the increase of tumor grade and disease stage,the expression of RIT1 had a tendency to increase.A total of 62 samples in 360 HCC samples had RIT1 gene mutation,and the mutation rate was about 17.2%.Survival curve analysis showed that the overall survival period of RIT1 high expression group and RIT1 mutation group was shorter than that of RIT1 low expression group and no mutation group(P<0.01).RAF proto-oncogene serine/threonine-protein kinase(RAF),neurotrophic receptor tyrosine kinase 1 (NTRK1),Ral GDP dissociation stimulator like 1 (RGL1),nerve growth factor (NGF),RLF zinc finger protein,Ral guanine nucleotide-dissociation stimulator (RalGDS),interferon-related developmental regulator 1 (IFRD1),RAS-related protein Rap-1 b (RAP1 B),Kelch like family member 12 (KLHL12),MLLT4,mothers against decapentaplegic homolog 3 (Smad3) and other proteins had obvious interactions with RIT1.STX6,MPZL1,PKM2,RNF24,SOAT1 and other proteins were co-expressed with RIT1 in HCC,these proteins were mainly involved in small G protein signal transduction,Ras signal pathway and neurotrophic factor TRK receptor signal pathway,which could promote DNA conformation changes,mitosis,cell cycle and so on.Conclusion RIT1 is highly expressed in HCC tissues and has a high frequency of gene mutation,which is related to poor prognosis of patients,providing a theoretical basis for further research on the role of RIT1 in the occurrence and development of HCC.
作者
张蓉
周泉
陈映红
黄率帅
ZHANG Rong;ZHOU Quan;CHEN Yinghong;HUANG Lvshuai(Department of Clinical Laboratory,General Hospitalof Southern Theatre Command,Guangzhou Guangdong510010,China)
出处
《华南国防医学杂志》
CAS
2021年第7期510-516,共7页
Military Medical Journal of South China
关键词
肝细胞癌
RIT1蛋白
表达
预后
Hepatocellular carcinoma
GTP-binding protein Rit1
Expression
Prognosis
作者简介
通讯作者:黄率帅,E-mail:76101505@qq.com
