摘要
[背景和目的]
膀胱癌是泌尿系统最常见的肿瘤,其中移行上皮细胞癌(BTCC)占94%,初次治疗后5年复发率高达50%-90%,约20%最终行膀胱全切术,致使患者生活质量显著下降,如何早期诊断与筛查以及有效预测其复发是目前迫切需要解决问题。
体液肿瘤标志物作为现有普查手段之一可大大提高癌症检出率,但是,现在肿瘤标志物存在检出谱系过窄、敏感性较低、用检标本难以反复采集的缺点,难以用于肿瘤的普查。尿液修饰核苷反映了机体RNA的代谢速率,且标本采集简单、无创伤,可以作为非常有发展潜力的肿瘤标志物。
本试验通过检测膀胱癌患者和正常人7种修饰核苷的水平差异,探讨尿液修饰核苷检测在膀胱移行细胞癌诊断中的意义与其生物学行为的相关性,从而为修饰核苷检测应用于膀胱癌筛查、诊断、预后监测、评估疗效提供理论和实验依据。
[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,Π级16例,Ш级7例；浸润性癌16例,非侵润癌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1-甲基腺苷(M1A)、N1-乙酰胞苷(ac4C)、腺嘌呤核苷(A)、06-甲基鸟苷(06-MeG)、5’-脱氧-5’-甲基硫代腺苷(MTA)、1-甲基次黄苷(1-MeI)和1-甲基鸟苷(1-MeG)七种修饰核苷水平(核苷含量/肌酐)。
[结果]
1:M1A.ac4C.06-MeG.1-MeI在膀胱癌患者尿中水平分别为4.61±1.82nmol,0.63±0.29nmol,0.46±0.35 nmol,12.28±9.74 nmol,均显著高于正常人的2.85±0.68 nmol,0.35±0.15nmol,0.21±0.11 nmol,5.39±2.41 nmol(P值均<0.01)；
2：诊断准确度由大到小为：1-MeI>M1A>ac4C>06-MeG,1-MeI与M1A联合检测即可达到对膀胱癌极高的灵敏度和特异性(灵敏度为92.45%,特异度为87.50%)。
3：膀胱移行细胞癌三级(I级,Π级,Ш级)之间患者这7种核苷含量并无显著性差别(P值均>0.05),侵润性与非侵润性之间也无显著性差别(P值均>0.05)。
4：复发患者尿中M1A和ac4C的水平分别为6.74±1.23 nmol,0.83±0.41 nmol,均显著性高于初发患者(3.93±1.43,0.57±0.20,P值均<0.05),并且M1A的含量与复发时间呈负相关(r=0.895,P<0.01)。
[结论]
1：1-甲基腺苷(M1A)、N·1-乙酰胞苷(ac4C)、06-甲基鸟苷(06-MeG)、1-甲基次黄苷(1-MeI)在膀胱癌患者尿中水平显著高于正常人,可作为筛选膀胱癌的分子标志物；
2：M1A联合1-MeI检测时有极高敏感性和特异性；提示这两种核苷联合检测将有助于确定膀胱癌高危人群
3：复发者M1A和ac4C水平显著高于初发者,且M1A的含量与复发时间呈负相关,提示检测尿液修饰核苷的浓度有助于监测预后、评估疗效。
Background and objective
Bladde cancer is the most common urothelial tumors, including transitional cell carcinoma of bladder (BTCC) accounted for 94%, five years recurrence rate is as high as 50%～90% after first treatment, about 20% must be operated cystectomy eventually, the quality of life of the patients descend significantly. It is an urgent problem needed to solve about predicted recurrence effectively, early diagnosis and screening.
Tumor marker in body fluids will help to find cancer in surver. However, most of tumor markers could not be well applied to survey and followed up cancer patients because of narrow detection scope and low sensitivity. As modified nucleosides reflect alter tRNA turnover which seems to be impaired in the body of cancer patients, they have been evaluated as potentoal tumor markers.
We detected the levels of urinary modified nucleosides in bladder cancer group and control group, which was indicated by the ratio of nucleosides to creatinine and explore the feasibility of urinary modified nucleosides as potential molecular markers and its relation to biological behavior of bladder transitional cell carcinoma(BTCC).
引文
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