基于Oncomine和TCGA数据挖掘分析MTERF2在胰腺癌中的表达及临床意义
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摘要
目的:探究人线粒体转录终止因子2(MTERF2)在胰腺癌中的表达及临床意义。方法:检索Oncomine数据库中的MTERF2信息,对其在胰腺癌组织和正常胰腺组织中的表达进行荟萃分析;从美国癌症基因组图谱(TCGA)中下载胰腺癌数据集MTERF2 RNA Seq V2数据及临床病理资料;利用R 2.15.3软件分析MTERF2表达量与临床病理参数的相关性及预后;利用Kaplan-Meier生存函数分析MTERF2表达量和胰腺癌患者预后的关联。结果:Oncomine数据库中共收集了586个不同类型的研究结果,其中关于MTERF2表达有统计学差异的研究有58个,MTERF2表达增高的研究有26个,表达减低的研究有32个。共有9项研究涉及MTERF2在胰腺癌组织和正常组织中的表达,包括226例临床样本,与对照组相比,MTERF2在胰腺癌中低表达(P=7.34×10-6)。TCGA胰腺癌数据集中共收集179例具有临床病理参数的病例及其对应的MTERF2 mRNA表达量。剔除病理参数不详或不完整的病例,利用R 2.15.3软件分析发现,MTERF2 mRNA表达量与胰腺癌患者T分期、M分期、癌症类型及原发部位存在显著相关(均P<0.05),而与患者的年龄、性别、N分期、AJCC病理分期、等级、组织学类型及饮酒史无显著相关(均P>0.05)。Kaplan-Meier生存分析发现,胰腺癌患者MTERF2的表达水平与总生存率(OS)无显著相关性(P>0.05),而与无病生存率(DFS)显著相关(P<0.001)。结论:Oncomine和TCGA数据挖掘显示,人MTERF2在胰腺癌组织中低表达,且MTERF2表达量与胰腺癌患者总生存率无显著相关性,与无病生存率有显著相关性。
Objective:To explore the expression of human mitochondrial transcription termination factor 2(MTERF2) and its clinic significance in pancreatic cancer.Methods:Data about human MTERF2 were retrieved from the Oncomine database and the role of MTERF2 in pancreatic cancer was analyzed. The expression of MTERF2 and clinical information in pancreatic cancer patients were downloaded from The Cancer Genome Atlas(TCGA) database by R 2.15.3 software. Then the relationship between the expression of MTERF2 mRNA and clinicopathological characteristics, and the prognostic value of MTERF2 expression were analyzed.Results:Totally,586 studies of different types relevant to the expression of MTERF2 were identified in the Oncomine database.The MTERF2 expression was statistically significant in 58 of the studies, overexpressed in 26 studies and underexpressed in 32 studies. A total of 9 studies were involved MTERF2 pancreatic cancer tissues and normal tissues,including a total of 226 samples. Overall, MTERF2 expression in pancreatic cancer tissues were lower than that in normal tissues. TCGA database was used to collect 179 cases with clinical pathological parameters and their corresponding MTERF2 expression levels. After the incomplete cases and those with no detailed pathological parameters were excluded, it was found that the expression level of MTERF2 mRNA was significantly correlated with the T stage, M stage, type of cancer, and primary site in patients with pancreatic by cancer R 2.15.3 software analysis. There was no significant correlation between age, sex, N stage, AJCC pathological stage, grade, histological type and drinking history. Kaplan-Meier survival analysis showed that there was no significant correlation between MTERF2 expression level and total survival rate in patients with pancreatic cancer, but a significant correlation with disease-free survival.Conclusion:Through the in-depth data mining of the TCGA cancer database and the Oncomine gene chip database, it is suggested that MTERF2 is lower expressed in pancreatic cancer, there was no significant correlation between MTERF2 expression level and total survival rate in patients with pancreatic cancer, but a significant correlation with disease-free survival.
Objective:To explore the expression of human mitochondrial transcription termination factor 2(MTERF2) and its clinic significance in pancreatic cancer.Methods:Data about human MTERF2 were retrieved from the Oncomine database and the role of MTERF2 in pancreatic cancer was analyzed. The expression of MTERF2 and clinical information in pancreatic cancer patients were downloaded from The Cancer Genome Atlas(TCGA) database by R 2.15.3 software. Then the relationship between the expression of MTERF2 mRNA and clinicopathological characteristics, and the prognostic value of MTERF2 expression were analyzed.Results:Totally,586 studies of different types relevant to the expression of MTERF2 were identified in the Oncomine database.The MTERF2 expression was statistically significant in 58 of the studies, overexpressed in 26 studies and underexpressed in 32 studies. A total of 9 studies were involved MTERF2 pancreatic cancer tissues and normal tissues,including a total of 226 samples. Overall, MTERF2 expression in pancreatic cancer tissues were lower than that in normal tissues. TCGA database was used to collect 179 cases with clinical pathological parameters and their corresponding MTERF2 expression levels. After the incomplete cases and those with no detailed pathological parameters were excluded, it was found that the expression level of MTERF2 mRNA was significantly correlated with the T stage, M stage, type of cancer, and primary site in patients with pancreatic by cancer R 2.15.3 software analysis. There was no significant correlation between age, sex, N stage, AJCC pathological stage, grade, histological type and drinking history. Kaplan-Meier survival analysis showed that there was no significant correlation between MTERF2 expression level and total survival rate in patients with pancreatic cancer, but a significant correlation with disease-free survival.Conclusion:Through the in-depth data mining of the TCGA cancer database and the Oncomine gene chip database, it is suggested that MTERF2 is lower expressed in pancreatic cancer, there was no significant correlation between MTERF2 expression level and total survival rate in patients with pancreatic cancer, but a significant correlation with disease-free survival.
引文
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[12]许斌,刘宁,陈恕求,等.基于ONCOMINE数据库分析I型5α还原酶在前列腺癌中的表达及意义[J].中华男科学杂志,2016,22(9):771-776.
[13]马小安,吴涛,郭卉,等.基于Oncomine、TCGA数据库挖掘p57、CKS1及SKP2在肝细胞癌肝癌中的表达及预后意义[J].临床医学研究与实践,2016,1(25):1-4.
[14]Hessmann E,Johnsen S A,Siveke J T,et al.Epigenetic treatment of pancreatic cancer:is there a therapeutic perspective on the horizon[J]?Gut,2017,66(1):168-179.
[15]Tumas J,Kvederaviciute K,Petrulionis M,et al.Metabolomics in pancreatic cancer biomarkers research[J].Med Oncol,2016,33(12):133-147.
[16]Carrato A,Falcone A,Ducreux M,et al.A systematic review of the burden of pancreatic cancer in Europe:real-world impact on survival,quality of life and costs[J].J Gastrointestinal Cancer,2015,46(3):201-211.
[17]王玮,孙哲,邓靖宇,等.基于多中心大样本数据库的胃癌外科治疗相关数据的整合与分析[J].中华胃肠外科杂志,2016,19(2):179-185.
[18]Roberti M,Polosa P L,Bruni F,et al.MTERF factors:a multifunction protein family[J].Biomol Concepts,2010,1(2):215-224.
[19]Shutt T E,Shadel G S.A compendium of human mitochondrial gene expression machinery with links to disease[J].Environ Mol Mutagenesis,2010,51(5):360-379.
[2]Siegel R,Ma J,Zou Z,et al.Cancer statistics,2014[J].CA Cancer J Clin,2014,64(1):9-29.
[3]陈瑶,何云刚,余敏,等.一个人类线粒体转录终止样因子基因的克隆[J].云南大学学报(自然科学版),2003,25(12):205-209.
[4]Xiong W,Huang W,Jiao Y,et al.Production,purification and characterization of mouse monoclonal antibodies against human mitochondrial transcription termination factor 2(MTERF2)[J].Protein Expr Purif,2010,82(1):11-19.
[5]杨勇琴,左绍远,张海洋,等.人线粒体转录终止因子2蛋白的生物信息学分析[J].现代生物医学进展,2016,16(5):944-949.
[6]孙美涛,张成桂,梅雯,等.人线粒体转录终止因子2(MTERF2)在Caski宫颈癌细胞的表达和定位[J].细胞与分子免疫学杂志,2017,33(6):783-788.
[7]Chen Y,Zhou G,Yu M,et al.Cloning and functional analysis of human m TERFL encoding a novel mitochondrial transcription termination factor-like protein[J].Biochem Biophys Res Commun,2005,337(4):1112-1118.
[8]Hyv?rinen A K,Pohjoism?ki J L,Holt I J,et al.Overexpression of MTERFD1 or MTERFD3 impairs the completion of mitochondrial DNA replication[J].Mol Biol Rep,2011,38(2):1321-1328.
[9]Huang W,Yu M,Jiao Y,et al.Mitochondrial transcription termination factor 2 binds to entire mitochondrial DNA and negatively regulates mitochondrial gene expression[J].Acta Biochim Biophys Sin(Shanghai),2011,43(6):472-479.
[10]孙美涛,梅雯,王唯斯,等.线粒体转录终止因子2对人子宫颈癌He La细胞线粒体基因表达的影响[J].生物技术,2016,28(1):36-43.
[11]Pellegrini M,Asin-Cayuela J,Erdjument-Bromage H,et al.MTERF2 is a nucleoid component in mammalian mitochondria[J].Biochim Biophys Acta,2009,1787(5):296-302.
[12]许斌,刘宁,陈恕求,等.基于ONCOMINE数据库分析I型5α还原酶在前列腺癌中的表达及意义[J].中华男科学杂志,2016,22(9):771-776.
[13]马小安,吴涛,郭卉,等.基于Oncomine、TCGA数据库挖掘p57、CKS1及SKP2在肝细胞癌肝癌中的表达及预后意义[J].临床医学研究与实践,2016,1(25):1-4.
[14]Hessmann E,Johnsen S A,Siveke J T,et al.Epigenetic treatment of pancreatic cancer:is there a therapeutic perspective on the horizon[J]?Gut,2017,66(1):168-179.
[15]Tumas J,Kvederaviciute K,Petrulionis M,et al.Metabolomics in pancreatic cancer biomarkers research[J].Med Oncol,2016,33(12):133-147.
[16]Carrato A,Falcone A,Ducreux M,et al.A systematic review of the burden of pancreatic cancer in Europe:real-world impact on survival,quality of life and costs[J].J Gastrointestinal Cancer,2015,46(3):201-211.
[17]王玮,孙哲,邓靖宇,等.基于多中心大样本数据库的胃癌外科治疗相关数据的整合与分析[J].中华胃肠外科杂志,2016,19(2):179-185.
[18]Roberti M,Polosa P L,Bruni F,et al.MTERF factors:a multifunction protein family[J].Biomol Concepts,2010,1(2):215-224.
[19]Shutt T E,Shadel G S.A compendium of human mitochondrial gene expression machinery with links to disease[J].Environ Mol Mutagenesis,2010,51(5):360-379.