利用Oncomine和TCGA数据集分析MTERF3在大肠腺癌的表达及预后作用
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摘要
目的基于数据挖掘探讨人线粒体转录终止因子3在正常肠组织和大肠腺癌中的表达水平,并探讨MTERF3 mRNA表达量与大肠腺癌患者临床病理参数的相关性及其预后作用。方法从Oncomine基因芯片数据库和美国癌症基因组图谱中下载关于大肠腺癌患者MTERF3 mRNA二代测序数据及临床病理资料,使用R 3.3.0软件分析MTERF3表达量与临床病理参数的相关性及其预后价值。结果Oncomine数据库中共收集了344个不同类型的肿瘤研究结果,关于MTERF3表达有统计学差异的研究结果共20项,其中MTERF3高表达的研究有19项,低表达的研究有1项(P<0.05)。数据库中共有7个不同的研究涉及MTERF3在大肠腺癌组织中和正常大肠组织中的表达,与正常肠组织相比,MTERF3在大肠腺癌中呈高表达,且差异具有统计学意义(P=1.56×10~(-23))。分析发现,349例大肠腺癌患者MTERF3表达水平与年龄、性别、肿瘤部位、浸润深度、淋巴转移、远处转移无关(P>0.05),与病理类型相关(P<0.05);Kaplan-Meier分析发现,大肠腺癌患者MTERF3的表达水平与总生存率(OS)和无病生存率(DFS)均无显著相关性(P>0.05)。结论人MTERF3在大肠腺癌组织中高表达,但MTERF3 mRNA表达量与大肠腺癌患者的预后无显著的相关性。
Objective To explore the expression of human mitochondrial transcription termination factor3(MTERF3) in colorectal adenocarcinoma and normal intestinal tissue based on the cancer genome atlas(TCGA) and Oncomine datasets.And elucidate the correlation between the expression of MTERF3 mRNA and the clinical pathological parameters of patients with colorectal adenocarcinoma and its prognosis.Methods Download the sequencing data of MTERF3 mRNA in colorectal adenocarcinoma tissues and clinical pathological data from the Oncomine gene chip database and TCGA.We analyzed the correlation between the expression of MTERF3 mRNA and the clinical pathological parameters and its prognosis by using the R3.3.0 software.Results Totally344 studies relevant to the expression of MTERF3 were identified in the Oncomine database.The MTERF3 expression was statistically difference in 20 studies,and over-expressed in 19 studies and down-regulated in only one study(P<0.05).A total of 7 studies involved the expression of MTERF3 in colorectal adenocarcinoma tissue and normal large intestine tissue,and the expression of MTERF3 in colorectal adenocarcinoma tissue was significantly higher than that in normal colorectal tissue(P = 1.56 × 10~(-23)).The expression of MTERF3 in colorectal adenocarcinoma was not related to age,sex,tumor location,depth of invasion,lymphatic metastasis,and was related to cancer types(P<0.05).Kaplan-meier analysis showed that there was no significant correlation between the expression of MTERF3 and overall survival rate(OS) and disease-free survival rate(DFS) in colorectal adenocarcinoma patients(P > 0.05).Conclusions MTERF3 was highly expressed in colorectal adenocarcinoma tissue.However,the expression level of MTERF3 protein was not significantly correlated with the prognosis of colorectal adenocarcinoma.
Objective To explore the expression of human mitochondrial transcription termination factor3(MTERF3) in colorectal adenocarcinoma and normal intestinal tissue based on the cancer genome atlas(TCGA) and Oncomine datasets.And elucidate the correlation between the expression of MTERF3 mRNA and the clinical pathological parameters of patients with colorectal adenocarcinoma and its prognosis.Methods Download the sequencing data of MTERF3 mRNA in colorectal adenocarcinoma tissues and clinical pathological data from the Oncomine gene chip database and TCGA.We analyzed the correlation between the expression of MTERF3 mRNA and the clinical pathological parameters and its prognosis by using the R3.3.0 software.Results Totally344 studies relevant to the expression of MTERF3 were identified in the Oncomine database.The MTERF3 expression was statistically difference in 20 studies,and over-expressed in 19 studies and down-regulated in only one study(P<0.05).A total of 7 studies involved the expression of MTERF3 in colorectal adenocarcinoma tissue and normal large intestine tissue,and the expression of MTERF3 in colorectal adenocarcinoma tissue was significantly higher than that in normal colorectal tissue(P = 1.56 × 10~(-23)).The expression of MTERF3 in colorectal adenocarcinoma was not related to age,sex,tumor location,depth of invasion,lymphatic metastasis,and was related to cancer types(P<0.05).Kaplan-meier analysis showed that there was no significant correlation between the expression of MTERF3 and overall survival rate(OS) and disease-free survival rate(DFS) in colorectal adenocarcinoma patients(P > 0.05).Conclusions MTERF3 was highly expressed in colorectal adenocarcinoma tissue.However,the expression level of MTERF3 protein was not significantly correlated with the prognosis of colorectal adenocarcinoma.
引文
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[15]Skrzypczak M,Goryca K,Rubel T,et al.Modeling Oncogenic Signaling in Colon Tumors by Multidirectional Analyses of Microarray Data Directed for Maximization of Analytical Reliability[J].Plos One,2010,5(10):e13091.
[16]Wang ZX,Cao JX,Liu ZP,et al.Combination of chemotherapy and immunotherapy for colon cancer in China:a meta-analysis[J].World journal of gastroenterology,2014,20(4):1095-1106.
[17]Mao Q,Zhang Y,Fu X,et al.A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy[J].Journal of Cancer Research&Clinical Oncology,2013,139(2):211-222.
[18]Day LW,Velayos F.Colorectal Cancer Screening and Surveillance in the Elderly:Updates and Controversies[J].Gut&Liver,2015,9(2):143.
[19]Linder T,Park CB,Asin-Cayuela J,et al.A family of putative transcription termination factors shared amongst metazoans and plants[J].Current Genetics,2005,48(4):265-269.
[20]Roberti M,Bruni F,Loguercio Polosa P,et al.MTERF3,the most conserved member of the m TERF-family,is a modular factor involved in mitochondrial protein synthesis[J].Biochim Biophys Acta,2006,1757(9-10):1199-1206.
[21]Spahr H,Samuelsson T,Hallberg BM,et al.Structure of mitochondrial Transcription termination factor 3 reveals a novel nucleic acidbinding domain[J].Biochem Biophys Res Commun,2010,397(3):386-390.
[22]熊伟,张晓娟,张海洋,等.基于生物信息学方法预测人线粒体转录终止因子3蛋白的结构与功能[J].生物技术通讯,2015,26(3):367-373.
[23]Xiong W,Luo Y,Zhang C,et al.Expression,purification of recombinant human mitochondrial transcription termination factor3(h MTERF3)and preparation of polyclonal antibody against h MTERF3[J].Appl Biochem Biotechnol,2012,167(8):2318-2319.
[24]Li Y,Weibing S,Liu H,et al.Mitochondrial DNA from colorectal cancer cells promotes the malignant phenotype of NIH3T3 cells[J].Cell Biol Int,2008,32(8):979-983.
[25]Higuchi M,Regulation of mitochondrial DNA content and cancer.Mitochondrion,2007,7(1-2):53-57.
[2]李道娟,李倩,贺宇彤.结直肠癌流行病学趋势[J].肿瘤防治研究,2015,42(3):305-310.
[3]Sanoff HK,Sargent DJ,Campbell ME,et al.Five-year data and prognostic factor analysis of oxailplatin and irinotecan combinations for advanced colorectal cancer:N9741[J].J Clin Oncol,2008,26(35):5721-5727.
[4]熊伟,余敏,左绍远.线粒体转录终止因子蛋白家族在线粒体基因表达中的调节作用[J].中国生物化学与分子生物学报,2015,31(3):223-231.
[5]Hyvrinen K,Pohjoismki JL,Holt IJ,et al.Overexpression of MTERFD1 or MTERFD3 impairs the completion of mitochondrial DNA replication[J].Mol Biol Rep,2011,38(2):1321-1328.
[6]Park CB,Asin-Cayuela J,Cámara Y,et al.MTERF3 is a negative regulator of mammalian mt DNA transcription[J].Cell,2007,130(2):273-285.
[7]Werdenberg A,Lagouge M,Bratic A,et al.MTERF3 regulates mitochondrial ribosome biogenesis in invertebrates and mammals[J].PLo S Genet,2013,9(1):e1003178.
[8]自加吉,杨勇琴,孙美涛,等.人线粒体转录终止因子3在胃癌组织中的表达及其意义[J].临床与实验病理学杂志,2017,33(1):84-86.
[9]自加吉,杨勇琴,孙美涛,等.非小细胞肺癌中人线粒体转录终止因子3的表达及临床病理学意义[J].医学研究生学报,2017,30(2):160-164.
[10]Zhang C,Wu N,Gao F,et al.MTERFD1 functions as an oncogene[J].Oncotarget,2016,8(9):1-8.
[11]Rhodes DR,Yu J,Shanker K,et al.ONCOMINE:a cancer microarray database and integrated data-mining platform[J].Neoplasia,2004,6(1):1-6.
[12]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.
[13]Hong Y,Downey T,Eu KW,et al.A‘metastasis-prone’signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics[J].Clinical&Experimental Metastasis,2010,27(2):83-90.
[14]Sabates-Bellver J,Van der Flier LG,de Palo M.et al.Transcriptome profile of human colorectal adenomas[J].Mol Cancer Res,2007,5(12):1263-1275.
[15]Skrzypczak M,Goryca K,Rubel T,et al.Modeling Oncogenic Signaling in Colon Tumors by Multidirectional Analyses of Microarray Data Directed for Maximization of Analytical Reliability[J].Plos One,2010,5(10):e13091.
[16]Wang ZX,Cao JX,Liu ZP,et al.Combination of chemotherapy and immunotherapy for colon cancer in China:a meta-analysis[J].World journal of gastroenterology,2014,20(4):1095-1106.
[17]Mao Q,Zhang Y,Fu X,et al.A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy[J].Journal of Cancer Research&Clinical Oncology,2013,139(2):211-222.
[18]Day LW,Velayos F.Colorectal Cancer Screening and Surveillance in the Elderly:Updates and Controversies[J].Gut&Liver,2015,9(2):143.
[19]Linder T,Park CB,Asin-Cayuela J,et al.A family of putative transcription termination factors shared amongst metazoans and plants[J].Current Genetics,2005,48(4):265-269.
[20]Roberti M,Bruni F,Loguercio Polosa P,et al.MTERF3,the most conserved member of the m TERF-family,is a modular factor involved in mitochondrial protein synthesis[J].Biochim Biophys Acta,2006,1757(9-10):1199-1206.
[21]Spahr H,Samuelsson T,Hallberg BM,et al.Structure of mitochondrial Transcription termination factor 3 reveals a novel nucleic acidbinding domain[J].Biochem Biophys Res Commun,2010,397(3):386-390.
[22]熊伟,张晓娟,张海洋,等.基于生物信息学方法预测人线粒体转录终止因子3蛋白的结构与功能[J].生物技术通讯,2015,26(3):367-373.
[23]Xiong W,Luo Y,Zhang C,et al.Expression,purification of recombinant human mitochondrial transcription termination factor3(h MTERF3)and preparation of polyclonal antibody against h MTERF3[J].Appl Biochem Biotechnol,2012,167(8):2318-2319.
[24]Li Y,Weibing S,Liu H,et al.Mitochondrial DNA from colorectal cancer cells promotes the malignant phenotype of NIH3T3 cells[J].Cell Biol Int,2008,32(8):979-983.
[25]Higuchi M,Regulation of mitochondrial DNA content and cancer.Mitochondrion,2007,7(1-2):53-57.