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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 investigate the diagnostic value of seven nucleosides M1A, ac4C, A, 06-MeG, MTA, 1-MeI and 1-MeG in the diagnosis and prognosis of bladder transitional cell carcinoma (BTCC). Methods Totally 45 cases of transitional cell carcinoma of the bladder were pathologically confirmed as bladder cancer group, of which 32 cases were newly diagnosed and 13 cases recurred. The histological grade was grade Ⅰ in 22 cases, grade Ⅱ in 16 cases and grade Ⅲ in 7 cases. The invasive carcinoma 16 cases, non-invasive cancer in 29 cases. Sixteen normal subjects were selected as control group. The levels of M1A, ac4C, A, 06-MeG and MTA in urine of bladder cancer and control groups were detected by HPLC / ESI-Q-TOF- 1-MeI, 1-MeG seven kinds of modified nucleoside levels (nucleoside content / creatinine). Results The urinary levels of M1A, ac4C, 06-MeG and 1-MeI in BTCC group were significantly higher than those in control group (4.61 ± 1.82, 0.63 ± 0.29, 0.46 ± 0.35, and (12.28 ± 9.74, (2.85 ± 0.68), (0.35 ± 0.15), (0.21 ± 0.11) and (5.39 ± 2.41), P <0.01]. The accuracy of diagnosis was 1-MeI> M1A> ac4C> 06-MeG , And the combined detection of 1-MeI and M1A can achieve the highest sensitivity and specificity for bladder cancer with 92.45% and 87.50% respectively. Urine modified nucleosides levels between BTCC histological grade and between infiltration and non-invasiveness were not statistically different (P> 0.05). The levels of M1A and ac4C in patients with recurrence were (6.74 ± 1.23) and (0.83 ± 0.41), respectively, which were significantly higher than those in the patients with initial recurrence (3.93 ± 1.43, 0.57 ± 0.20, P <0.05) The recurrence time was negatively correlated (r = -0.895, P <0.01). Conclusion The combination of urine M1A and 1-MeI is of great significance in the diagnosis of BTCC. M1A and ac4C are helpful to predict the prognosis of bladder transitional cell carcinoma.