尿中修饰核苷水平在膀胱移行细胞癌诊断及预测预后中的意义  

Significance of urine modified nucleoside levels in diagnosis and prognosis of bladder transitional cell carcinoma

作　　者：吴辉[1] 刘宏民[2] 杨松鹏[1] 王庆伟[1] 张玉瑞[1] 袁璞[1] 易强[1] 刘刚[1] 王少敏[2] 宋东奎[1,3,4] 

机构地区：[1]郑州大学第一附属医院泌尿外科,郑州450052 [2]郑州大学化学系质谱实验室,郑州450052 [3]郑州大学肿瘤分子外科研究所,郑州450052 [4]河南省高等学校临床医学重点学科开放实验室

出　　处：《第三军医大学学报》2011年第16期1714-1717,共4页Journal of Third Military Medical University

基　　金：河南省科技攻关项目(72102310106)~~

摘　　要：目的探讨尿中7种修饰核苷M1A、ac4C、A、06-MeG、MTA、1-MeI、1-MeG检测在膀胱移行细胞癌(bladdertransitional cell carcinoma,BTCC)诊断及预测预后中的意义。方法选取经病理证实为膀胱移行细胞癌患者45例为膀胱癌组,其中初发32例,复发13例;组织学分级:Ⅰ级22例,Ⅱ级16例,Ⅲ级7例;浸润性癌16例,非浸润癌29例。选取16例正常人为对照组。应用高效液相色谱/电喷雾-四极杆-飞行时间质谱技术(HPLC/ESI-Q-TOF-MS)检测膀胱癌组和对照组尿液中M1A、ac4C、A、06-MeG、MTA、1-MeI、1-MeG 7种修饰核苷水平(核苷含量/肌酐)。结果 BTCC组尿液M1A、ac4C、06-MeG和1-MeI水平[分别为(4.61±1.82)、(0.63±0.29)、(0.46±0.35)和(12.28±9.74)],均显著高于对照组[(2.85±0.68)、(0.35±0.15)、(0.21±0.11)和(5.39±2.41),P<0.01];诊断准确度由大到小为1-MeI>M1A>ac4C>06-MeG,且1-MeI与M1A联合检测可达到对膀胱癌最高的灵敏度和特异性,分别为92.45%和87.50%。BTCC组织学分级之间以及浸润性与非浸润性之间尿液修饰核苷水平差异均无统计学意义(P>0.05)。复发患者尿液M1A和ac4C水平分别为(6.74±1.23)、(0.83±0.41),均显著性高于初发患者[(3.93±1.43)、(0.57±0.20),P<0.05],M1A与其复发时间呈负相关(r=-0.895,P<0.01)。结论尿液M1A联合1-MeI检测在膀胱移行细胞癌诊断中意义重大,M1A和ac4C有助于预测膀胱移行细胞癌患者预后。Objective To study the significance of the levels of modified nucleosides M1A,ac4C,A,06-MeG,MTA,1-MeI,and 1-MeG in urine in the diagnosis and prognosis of bladder transitional cell carcinoma（BTCC）.Methods We enrolled 45 patients with BTCC confirmed by pathological examination as a BTCC group and 16 healthy volunteers as a control group.The 45 patients（32 primary cases and 13 recurrent cases） included 22 cases of histological grade Ⅰ,16 of histological grade Ⅱ,and 7 of histological grade Ⅲ,with 16 cases of invasive carcinoma and 29 of noninvasive carcinoma.High-performance liquid chromatography/electrospray ionization-quadrupole-time-of-flight mass spectrometry（HPLC/ESI-Q-TOF-MS） was used to measure the levels of M1A,ac4C,A,06-MeG,MTA,1-MeI,and 1-MeG in the urine of the BTCC group and control group,indicated by the concentration ratio of the nucleosides to creatinine.Results The levels of M1A,ac4C,06-MeG,and 1-MeI in the urine of the BTCC group were 4.61±1.82,0.63±0.29,0.46±0.35,and 12.28±9.74,respectively,significantly higher than those of the control group（2.85±0.68,0.35±0.15,0.21±0.11,and 5.39±2.41,respectively）（P0.05）.The urine 1-MeI level was the most accurate indicator for diagnosing BTCC,followed by M1A,ac4C,and 06-MeG.A combination of urine M1A and 1-MeI levels had the highest sensitivity（92.45%） and the highest specificity（87.50%） for diagnosing BTCC.There was no significant differences in the urine modified nucleoside levels among the patients of histological grade Ⅰ,Ⅱ,and Ⅲ and between the patients with invasive and noninvasive carcinoma.The levels of M1A and ac4C in the urine from the recurrent patients were 6.74±1.23 and 0.83±0.41,significantly higher than those from the primary patients（3.92±1.43 and 0.57±0.20）（P0.05）.The urine M1A level was negatively correlated with the recurrent time（r=-0.895,P0.01）.Conclusion A combination of urine M1A and 1-MeI levels is of great importance for the diagnosis of BTCC.The urine M1A and ac4C levels are

关 键 词：膀胱移行细胞癌 修饰核苷 高效液相色谱/电喷雾-四极杆-飞行时间质谱技术 

分 类 号：R730.43[医药卫生—肿瘤] R737.14[医药卫生—临床医学]