PRC1基因表达对膀胱癌患者临床病理特征及预后的影响
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摘要
目的探讨PRC1基因表达对膀胱癌患者临床病理特征及预后的影响。方法在GEO数据库中下载膀胱癌样本资料GSE13507和相关临床信息。通过非配对t检验PRC1在正常膀胱组织与膀胱癌组织中的表达差异;采用卡方检验研究PRC1基因表达与膀胱癌患者临床病理特征的相关性;Log-rank法进行生存分析比较;运用基因集富集分析(gene set enrichment analysis,GSEA)的方法预测PRC1调控膀胱癌细胞的相关通路。结果 PRC1在膀胱癌细胞中高表达(P<0.0001);在癌细胞的肌层浸润性、T分期、N分期、肿瘤分级和有无癌症进展方面PRC1高表达的膀胱癌患者明显较低表达患者严重(P<0.05);PRC1高表达患者的总生存期和肿瘤特异性生存期显著低于低表达患者(P<0.05);GSEA的结果显示PRC1可能通过调节精子发生、E2MF信号通路和G2M检查点、未折叠蛋白反应、mTORC1信号通路、MYC-V2信号通路、MYC-V1信号通路、P13K-AKT-mTOR信号通路、有丝分裂纺锤体、胆固醇动态平衡和糖酵解等影响膀胱癌的发生发展。结论 PRC1可能作为膀胱癌的新治疗靶点或潜在的肿瘤标志物来判断患者的预后情况。
Objective To investigate the influence of PRC1 expression on the clinicopathologic characteristics and prognosis of patients with bladder cancer(BC).Methods The dataset GSE13507 was obtained from GEO database.Unpaired t-test was conducted to estimate the expression of PRC1 in normal bladder tissue and BC cells.Chi-square test was carried out to analyze the relationships between the PRC1 expression levels and clinical features of patients who suffered from BC.Log-rank based survival analysis was performed to the survivals in patients with BC.GSEAwas conductedtoexplorethe gene sets enrichedin PRC1 high-expression samples.Results Compared with the levels in normal bladder tissues,PRC1 mRNA levels was increased in BCs.Patients in PRC1 high expression group were correlative with worse clinicopathological characteristics(including gender,age,progression,muscular infiltration,T stage,N stage,and tumor grade)compared with those in PRC1 low expression group.PRC1 high expression was associated with worse prognosis in terms of cancer specific survival and overall survival.The results of GSEA showed that PRC1 might affect the occurrence and development of BC by regulating spermatogenesis,G2 Mcheckpoint and,E2 Fsignaling,unfolded-protein-respond,mTORC1 signaling,MYC_TARGETS_V2,MYC_TARGETS_V1,P13 K-AKT-mTOR signaling,mitotic spindle,cholesterol homeostasis and glycolysis.Conclusion PRC1 may make sense in prognosis and treatment of BC as potential marker and target.
Objective To investigate the influence of PRC1 expression on the clinicopathologic characteristics and prognosis of patients with bladder cancer(BC).Methods The dataset GSE13507 was obtained from GEO database.Unpaired t-test was conducted to estimate the expression of PRC1 in normal bladder tissue and BC cells.Chi-square test was carried out to analyze the relationships between the PRC1 expression levels and clinical features of patients who suffered from BC.Log-rank based survival analysis was performed to the survivals in patients with BC.GSEAwas conductedtoexplorethe gene sets enrichedin PRC1 high-expression samples.Results Compared with the levels in normal bladder tissues,PRC1 mRNA levels was increased in BCs.Patients in PRC1 high expression group were correlative with worse clinicopathological characteristics(including gender,age,progression,muscular infiltration,T stage,N stage,and tumor grade)compared with those in PRC1 low expression group.PRC1 high expression was associated with worse prognosis in terms of cancer specific survival and overall survival.The results of GSEA showed that PRC1 might affect the occurrence and development of BC by regulating spermatogenesis,G2 Mcheckpoint and,E2 Fsignaling,unfolded-protein-respond,mTORC1 signaling,MYC_TARGETS_V2,MYC_TARGETS_V1,P13 K-AKT-mTOR signaling,mitotic spindle,cholesterol homeostasis and glycolysis.Conclusion PRC1 may make sense in prognosis and treatment of BC as potential marker and target.
引文
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[19]刘宝琴,王华芹.内质网应激与未折叠蛋白反应的研究进展[J].中华肿瘤防治杂志,2010,18(11):869-872.
[20]别黎,张博,赵刚.有丝分裂纺锤体检验点基因在肿瘤中的作用研究进展[J].中华临床医师杂志,2012,6(2):436-438.
[2]陈锦超,王华.T1期膀胱癌行二次电切的意义及后续治疗的选择[J].中国肿瘤,2017,96(14):982-985.
[3] Miyazaki J,Nishiyama H.Epidemiology of urothelial carcinoma[J].Int J Urol,2017,24(10):730-734.
[4]施晓婷,张斌,邹晓平.PRC1在细胞分裂及肿瘤发生中的作用[J].现代肿瘤医学,2016,24(23):3860-3863.
[5]韩兆冬,罗宏伟,林卓远,等.PRC1高表达与前列腺癌生化复发的相关性研究[J].新医学,2016,47(7):442-446.
[6] Kim WJ,Kim EJ,Kim SK,et al.Predictive value of progression-related gene classifier in primary non-muscle invasive bladdercancer[J].Mol cancer,2010,9:3-3.
[7] Lee JS,Leem SH,Lee SY,et al.Expression signature of E2F1and itsassociated genes predict superficial to invasive progression of bladdertumors[J].J Clin Oncol,2010,28(16):2660-2667.
[8] Subramanian A,Tamayo P,Mootha VK,et al.Gene set en-richment analysis:a knowledge-based approach for interpretinggenome-wide expression profiles[J].Proc Natl Acad Sci USA,2005,102(43):15545-15550.
[9] Mootha VK,Lindgren CM,Eriksson KF,et al.PGC-1alpha-respon-sive genes involved in oxidative phosphorylation are coor-dinately downregulated in human diabetes[J].Nat Genet,2003,34(3):167-273.
[10] Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[11] Kamat AM,Hahn NM,Efstathiou JA,et al.Bladder cancer[J].Lancet,2016,388(10061):2796-2810.
[12]朱长军.PRC1在细胞胞质分裂过程中作用机理的研究[D].山东:山东大学,2008.
[13]康新迪,李婉玉.微管相关蛋白1通过Wnt/β-catenin信号通路促进肝细胞癌的早期复发[J].临床肝胆病杂志,2016,04:792-792.
[14]刘卓,杨为民,陈志强.E2F-1、E2F-3在膀胱癌组织的表达及临床意义[J].临床泌尿外科杂志,2007,24(1):60-62.
[15]焦勇,张波,李瑞晓,等.E2F3在浸润性膀胱癌中的表达关系以及对患者生存的影响[J].中国医师杂志,2016,18(1)1:29-32.
[16] Houtpraaf JH,Versmissen J,van derGiessen WJ.A concise re-view of DNA damage checkpoints and repair in mammalian cells[J].Cardiovasc RevascMed,2006,7(3):165-172.
[17] Kastan MB,Bartck J.Cell-cycle checkpoints and cancer[J].Nature,2004,432(7015):316-323.
[18]李明,丁健,缪泽鸿.未折叠蛋白反应的信号转导[J].生命科学,2008,20(2):246-252.
[19]刘宝琴,王华芹.内质网应激与未折叠蛋白反应的研究进展[J].中华肿瘤防治杂志,2010,18(11):869-872.
[20]别黎,张博,赵刚.有丝分裂纺锤体检验点基因在肿瘤中的作用研究进展[J].中华临床医师杂志,2012,6(2):436-438.