基于数据挖掘分析GOLM1基因在前列腺癌中的表达及其临床意义
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摘要
目的探讨GOLM1基因在前列腺癌中的表达及临床意义。方法利用Oncomine数据库分析GOLM1基因在前列腺癌与其癌旁正常组织组织中的表达情况,从TCGA数据库中下载相关的RNA-Seq数据和临床资料,分析GOLM1基因表达与患者临床病理学特征及预后的关系。结果 Oncomine及TCGA数据库分析结果显示,GOLM1基因在前列腺癌组织中的表达显著高于癌旁正常组织(P<0.001)。相关分析结果显示,TCGA数据库中547例前列腺癌患者GOLM1 mRNA表达水平与其年龄、临床T分期、病理学T分期及Gleason评分的相关性不大;低表达GOLM1基因的患者总生存期显著较高表达者长(HR=4.50,95%CI:3.77～5.37,P=0.038);ROC曲线分析显示最佳截断点为8.889,灵敏度为80.5%,特异度为80.8%,ROC曲线下面积为0.862(95%CI:0.813～0.912)。结论 GOLM1基因在前列腺癌组织中高表达,且与患者不良预后相关,可作为前列腺癌较好的诊断标志物。
Objective To investigate the expression of GOLM1 gene in prostate cancer and its clinical significance. Methods The Oncomine database was used to analyze the expression of GOLM1 gene in prostate cancer and normal prostate tissues. RNA-Seq data and clinical data downloaded from TCGA data,was analyzed the correlation between GOLM1 gene expression and clinicopathological features and prognosis. Results The analysis of Oncomine and TCGA databases showed that the expression of GOLM1 gene in prostate cancer tissues was significantly higher than that in normal prostate tissues(P<0.001). By analyzing the clinical data in 547 patients,it was found that the expression level of GOLM1 gene was not significantly correlated with age,Clinical T stage,Pathological T stage,and Gleason score. Kaplan-Meier analysis found that low expression of GOLM1 gene patients with overall survival was significantly longer than those with high expression(HR=4.50,95%CI:3.77-5.37,P=0.038). ROC curve analysis showed that the best cutoff point was 8.889,the sensitivity was 80.5%,the specificity was 80.8%,and the area under the ROC cwrve was 0.530(95%CI:0.813-0.912). Conclusions The GOLM1 gene is highly expressed in prostate cancer tissues and its expression level is related to poor prognosis. GOLM1 mRNA can be used as a candidate prostate cancer marker.
Objective To investigate the expression of GOLM1 gene in prostate cancer and its clinical significance. Methods The Oncomine database was used to analyze the expression of GOLM1 gene in prostate cancer and normal prostate tissues. RNA-Seq data and clinical data downloaded from TCGA data,was analyzed the correlation between GOLM1 gene expression and clinicopathological features and prognosis. Results The analysis of Oncomine and TCGA databases showed that the expression of GOLM1 gene in prostate cancer tissues was significantly higher than that in normal prostate tissues(P<0.001). By analyzing the clinical data in 547 patients,it was found that the expression level of GOLM1 gene was not significantly correlated with age,Clinical T stage,Pathological T stage,and Gleason score. Kaplan-Meier analysis found that low expression of GOLM1 gene patients with overall survival was significantly longer than those with high expression(HR=4.50,95%CI:3.77-5.37,P=0.038). ROC curve analysis showed that the best cutoff point was 8.889,the sensitivity was 80.5%,the specificity was 80.8%,and the area under the ROC cwrve was 0.530(95%CI:0.813-0.912). Conclusions The GOLM1 gene is highly expressed in prostate cancer tissues and its expression level is related to poor prognosis. GOLM1 mRNA can be used as a candidate prostate cancer marker.
引文
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[20]MARRERO J A,ROMANO P R,NIKOLAEVA O,et al.GP73,a resident Golgi glycoprotein,is a novel serum marker for hepatocel-lular carcinoma[J].J Hepatol,2005,43(6):1007-1012.
[21]LIU G,ZHANG Y,HE F,et al.Expression of GOLPH2 is associated with the progression of and poor prognosis in gastric cancer[J].Oncol Rep,2014,32(5):2077-2085.
[22]ZHANG Y,HU W,WANG L,et al.Association of GOLPH2 expression with survival in non-small-cell lung cancer:clinical implications and biological validation[J].Biomark Med,2017,11(11):967-977.
[23]LI W,WANG X,LI B,et al.Diagnostic significance of overexpression of Golgi membrane protein 1 in prostate cancer[J].Urology,2012,80(4):952,e951-957.
[24]YAN G,RU Y,WU K,et al.GOLM1 promotes prostate cancer progression through activating PI3K-AKT-mTOR signaling[J].Prostate,2018,78(3):166-177.
[2]韩苏军,张思维,陈万青,等.中国前列腺癌发病现状和流行趋势分析[J].临床肿瘤学杂志,2013,18(4):330-334.
[3] TABAYOYONG W,ABOUASSALY R.Prostate Cancer Screening and the Associated Controversy[J]. Surg Clin North Am,2015,95(5):1023-1039.
[4] BYRNE A M,BEKIARIS S,DUGGAN G,et al.Golgi phosphoprotein2(GOLPH2)is a novel bile acid-responsive modulator of oesophageal cell migration and invasion[J].Br J Cancer,2015,113(9):1332-1342.
[5] DUAN J,LI X,HUANG S,et al.GOLPH2,a gene downstream of ras signaling,promotes the progression of pancreatic ductal adenocarcinoma[J].Mol Med Rep,2018,17(3):4187-4194.
[6] VARAMBALLY S,LAXMAN B,MEHRA R,et al.Golgi protein GOLM1is a tissue and urine biomarker of prostate cancer[J].Neo-plasia,2008,10(11):1285-1294.
[7] KRISTIANSEN G,FRITZSCHE F R,WASSERMANN K,et al.GOLPH2protein expression as a novel tissue biomarker for prostate cancer:implications for tissue-based diagnostics[J].Br J Cancer,2008,99(6):939-948.
[8]郑玉平,陆峰泉,刘奎,等.GP73检测用于前列腺癌实验室诊断的价值[J].江苏医药,2016,42(8):968-969.
[9] ARREDOUANI M S,LU B,BHASIN M,et al.Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer[J]. Clin Cancer Res,2009,15(18):5794-5802.
[10] GRASSO C S,WU Y M,ROBINSON D R,et al.The mutational landscape of lethal castration-resistant prostate cancer[J].Nature,2012,487(7406):239-243.
[11]LAPOINTE J,LI C,HIGGINS J P,et al.Gene expression profiling identifies clinically relevant subtypes of prostate cancer[J].Proc Natl Acad Sci USA,2004,101(3):811-816.
[12]LIU P,RAMACHANDRAN S,ALI SEYED M,et al.Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells[J].Cancer Res,2006,66(8):4011-4019.
[13]LUO J H,YU Y P,CIEPLY K,et al.Gene expression analysis of prostate cancers[J].Mol Carcinog,2002,33(1):25-35.
[14]TAYLOR B S,SCHULTZ N,HIERONYMUS H,et al.Integrative genomic profiling of human prostate cancer[J].Cancer Cell,2010,18(1):11-22.
[15]TOMLINS S A,MEHRA R,RHODES D R,et al.Integrative molecular concept modeling of prostate cancer progression[J].Nat Genet,2007,39(1):41-51.
[16]VANAJA D K,CHEVILLE J C,ITURRIA S J,et al.Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression[J].Cancer Res,2003,63(14):3877-3882.
[17]VARAMBALLY S,YU J,LAXMAN B,et al.Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression[J].Cancer Cell,2005,8(5):393-406.
[18]KLADNEY R D,BULLA G A,GUO L,et al.GP73,a novel Golgilocalized protein upregulated by viral infection[J].Gene,2000,249(1):53-65.
[19]谢红彬,宫钰,彭涛.高尔基体驻膜糖蛋白GP73启动子克隆[J].安徽农业科学,2008(24):10359-10361,10401.
[20]MARRERO J A,ROMANO P R,NIKOLAEVA O,et al.GP73,a resident Golgi glycoprotein,is a novel serum marker for hepatocel-lular carcinoma[J].J Hepatol,2005,43(6):1007-1012.
[21]LIU G,ZHANG Y,HE F,et al.Expression of GOLPH2 is associated with the progression of and poor prognosis in gastric cancer[J].Oncol Rep,2014,32(5):2077-2085.
[22]ZHANG Y,HU W,WANG L,et al.Association of GOLPH2 expression with survival in non-small-cell lung cancer:clinical implications and biological validation[J].Biomark Med,2017,11(11):967-977.
[23]LI W,WANG X,LI B,et al.Diagnostic significance of overexpression of Golgi membrane protein 1 in prostate cancer[J].Urology,2012,80(4):952,e951-957.
[24]YAN G,RU Y,WU K,et al.GOLM1 promotes prostate cancer progression through activating PI3K-AKT-mTOR signaling[J].Prostate,2018,78(3):166-177.