1 暨南大学附属第一医院泌尿外科，广州 510632
目的：阐述胸苷磷酸化酶(thymidine phosphorylase，TYMP)基因在肾透明细胞癌(clear cell renal cell carcinoma，CCRCC)中的表达及临床意义。方法：利用Oncomine及GEPIA数据库分析TYMP基因在正常肾组织及CCRCC组织中的表达差异；通过GEPIA数据库进行TYMP基因表达程度与病理分期的相关性分析；利用OncoLnc数据库对TYMP基因的表达水平与CCRCC患者生存率作Kaplan-Meier生存分析和log-rank检验；经MethHC 数据库分析CCRCC组织和正常肾组织中TYMP启动子区DNA甲基化水平的差异；利用String-DB数据库分析与TYMP蛋白相互作用的蛋白；最后通过The Human Protein Atlas数据库分析TYMP蛋白在正常肾组织及CCRCC组织中的表达差异。结果：在mRNA及蛋白水平上，TYMP在CCRCC组织较正常肾组织中显著高表达，且TYMP mRNA表达水平越高，CCRCC病理分期越高；与TYMP基因低表达组相比，TYMP基因高表达的CCRCC患者总体生存率明显降低；CCRCC组织中TYMP启动子区DNA甲基化水平较正常组织甲基化水平显著降低；同时，与TYMP蛋白相关的蛋白有TK2，NT5M，CDA，UPRT，NT5C，UPP2，UMPS，TK1，UPP1和DPYD等，主要参与嘧啶核苷的合成、分解、代谢，转移戊糖基、蛋白质同源聚合等生物过程。结论：大样本数据挖掘能迅速获取CCRCC组织中TYMP基因表达的相关信息，为深入研究TYMP基因在CCRCC发生发展中的作用机制及预后奠定基础。关键词： 胸苷磷酸化酶；肾透明细胞癌；数据挖掘；甲基化
Expression and clinical significance of TYMP in clear cell renal cell carcinoma
CorrespondingAuthor:CHEN Jie Email: email@example.com
Foundation: The work was supported by National Natural Science Foundation, China (81871155).
Objective: To elucidate the expression and clinical significance of thymidine phosphorylase (TYMP) gene in clear cell renal cell carcinoma (CCRCC). Methods: Oncomine and GEPIA databases were used to analyze the expression of TYMP gene in normal kidney tissues and CCRCC tissues. The GEPIA database was used to analyze the relationship between the expression of TYMP gene and the pathological stage. The expression level of TYMP gene and survival rate of CCRCC patients were analyzed by Kaplan-Meier and log-rank test in OncoLnc database. The difference of DNA methylation level in TYMP promoter region between CCRCC tissue and normal kidney tissue was analyzed by MethHC database. The String-DB database was used to analyze the proteins with the TYMP protein. Finally, the expression of TYMP protein in normal kidney tissues and CCRCC tissues was analyzed by the Human Protein Atlas database. Results: At the mRNA and protein levels, TYMP was significantly higher in CCRCC tissues than that in normal kidney tissues, and the higher the expression level of TYMP mRNA, the higher the pathological stage of CCRCC. Compared with the low expression group of TYMP gene, the overall survival rate of patients with high expression of TYMP gene was significantly lower , the DNA methylation level of TYMP promoter region in CCRCC tissues was significantly lower than that in normal tissues . TYMP related proteins were TK2, NT5M, CDA, UPRT, NT5C, UPP2, UMPS, TK1, UPP1 and DPYD, which were involved in the synthesis, decomposition, metabolism, transfer of pentose groups, protein homopolymerization and other biological processes. Conclusion: Large sample data mining can quickly obtain the relevant information of TYMP gene expression in CCRCC tissues, which lays a foundation for further study on the mechanism and prognosis of TYMP gene in the development of CCRCC.Keywords： thymidine phosphorylase; clear cell renal cell carcinoma; data mining; methylation