采用基质辅助激光解吸电离飞行时间质谱肽组学分析法对血清和前列腺按摩后尿液标本进行分析，以鉴定前列腺癌生物标志物。
MALDI-TOF peptidomic analysis of serum and post-prostatic massage urine specimens to identify prostate cancer biomarkers.
作者信息
Padoan Andrea, Basso Daniela, Zambon Carlo-Federico, Prayer-Galetti Tommaso, Arrigoni Giorgio, Bozzato Dania, Moz Stefania, Zattoni Filiberto, Bellocco Rino, Plebani Mario
机构信息
1Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padua, Italy.
2Department of Biomedical Sciences, University of Padova, Padua, Italy.
出版信息
Clin Proteomics. 2018 Jul 25;15:23. doi: 10.1186/s12014-018-9199-8. eCollection 2018.
BACKGROUND
Lower urinary tract symptoms (LUTS) and prostate specific antigen-based parameters seem to have only a limited utility for the differential diagnosis of prostate cancer (PCa). MALDI-TOF/MS peptidomic profiling could be a useful diagnostic tool for biomarker discovery, although reproducibility issues have limited its applicability until now. The current study aimed to evaluate a new MALDI-TOF/MS candidate biomarker.
METHODS
Within- and between-subject variability of MALDI-TOF/MS-based peptidomic urine and serum analyses were evaluated in 20 and 15 healthy donors, respectively. Normalizations and approaches for accounting below limit of detection (LOD) values were utilized to enhance reproducibility, while Monte Carlo experiments were performed to verify whether measurement error can be dealt with LOD data. Post-prostatic massage urine and serum samples from 148 LUTS patients were analysed using MALDI-TOF/MS. Regression-calibration and simulation and extrapolation methods were used to derive the unbiased association between peptidomic features and PCa.
RESULTS
Although the median normalized peptidomic variability was 24.9%, the within- and between-subject variability showed that median normalization, LOD adjustment, and log data transformation were the best combination in terms of reliability; in measurement error conditions, intraclass correlation coefficient was a reliable estimate when the LOD/2 was substituted for below LOD values. In the patients studied, 43 peptides were shared by the urine and serum, and several features were found to be associated with PCa. Only few serum features, however, show statistical significance after the multiple testing procedures were completed. Two serum fragmentation patterns corresponded to the complement C4-A.
CONCLUSIONS
MALDI-TOF/MS serum peptidome profiling was more efficacious with respect to post-prostatic massage urine analysis in discriminating PCa.
背景
下尿路症状（LUTS）和基于前列腺特异性抗原的参数对于前列腺癌（PCa）的鉴别诊断似乎仅有有限的作用。基质辅助激光解吸电离飞行时间质谱（MALDI-TOF/MS）肽组学分析可能是一种用于发现生物标志物的有用诊断工具，尽管可重复性问题至今限制了其应用。本研究旨在评估一种新的MALDI-TOF/MS候选生物标志物。
方法
分别在20名和15名健康供体中评估基于MALDI-TOF/MS的肽组学尿液和血清分析的受试者内和受试者间变异性。采用归一化方法和处理低于检测限（LOD）值的方法来提高可重复性，同时进行蒙特卡洛实验以验证测量误差能否通过LOD数据处理。使用MALDI-TOF/MS分析148名下尿路症状患者的前列腺按摩后尿液和血清样本。采用回归校准以及模拟和外推方法来推导肽组学特征与前列腺癌之间的无偏关联。
结果
尽管归一化肽组学变异性的中位数为24.9%，但受试者内和受试者间变异性表明，就可靠性而言，中位数归一化、LOD调整和对数数据转换是最佳组合；在测量误差条件下，当用LOD/2替代低于LOD的值时，组内相关系数是一个可靠的估计值。在所研究的患者中，尿液和血清共有43种肽，并且发现一些特征与前列腺癌相关。然而，在完成多重检验程序后，只有少数血清特征具有统计学意义。两种血清碎片模式与补体C4-A相对应。
结论
在鉴别前列腺癌方面，MALDI-TOF/MS血清肽组学分析相对于前列腺按摩后尿液分析更有效。
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