Mao Yong, Zhao Xiaoping, Wang Shufang, Cheng Yiyu
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310027, PR China.
Anal Chim Acta. 2007 Aug 13;598(1):34-40. doi: 10.1016/j.aca.2007.07.038. Epub 2007 Jul 21.
Urinary nucleosides are potential biomarkers for many kinds of cancers. But up to now, it has been little focused in bladder cancer recognition. The aim of present study is try to validate the potential of urinary nucleoside as biomarker for bladder cancer diagnosis by finding out some urinary nucleosides with good discriminative performance for bladder cancer recognition in urinary nucleoside profile.
20 urinary samples for cancer and the same number for control are collected and treated by capillary electrophoresis-mass spectrometry experiments to achieve urinary nucleoside profile, in which 44 peaks were integrated and the ratios of the relative peak area to the concentration of urinary creatinine were used as features to describe all samples. Support vector machine based recursive feature elimination (SVM-RFE) and a new feature selection method called support vector machine based partial exhaustive search algorithm (SVM-PESA) were used for biomarker identification and seeking optimal feature subsets for bladder cancer recognition.
Based on the urinary nucleoside profile, 22 optimal feature subsets consist of 3-4 features were found with 95% 5-fold cross validation accuracy, 100% sensitivity and 90% specificity by SVM-PESA, whose performance were much better than that of optimal feature subset selected by SVM-RFE. By analyzing the statistical histogram of features' appearance frequency in several best feature subsets, urinary nucleosides with m/z 317, 290 and 304 were thought as potential biomarkers for bladder cancer recognition.
These results indicated urinary nucleosides may be useful as tumor biomarkers for bladder cancer, and the new method for biomarker selection is effective.
尿核苷是多种癌症的潜在生物标志物。但截至目前,其在膀胱癌识别方面的研究较少。本研究旨在通过在尿核苷谱中找出对膀胱癌识别具有良好判别性能的尿核苷,来验证尿核苷作为膀胱癌诊断生物标志物的潜力。
收集20份癌症患者的尿液样本和相同数量的对照样本,通过毛细管电泳-质谱实验进行处理以获得尿核苷谱,其中整合了44个峰,并将相对峰面积与尿肌酐浓度的比值用作描述所有样本的特征。基于支持向量机的递归特征消除法(SVM-RFE)和一种新的特征选择方法——基于支持向量机的部分穷举搜索算法(SVM-PESA),用于生物标志物识别和寻找用于膀胱癌识别的最佳特征子集。
基于尿核苷谱,通过SVM-PESA发现了由3至4个特征组成的22个最佳特征子集,其在95%的5折交叉验证准确率、100%的灵敏度和90%的特异性方面表现出色,其性能远优于通过SVM-RFE选择的最佳特征子集。通过分析几个最佳特征子集中特征出现频率的统计直方图,认为质荷比为317、290和304的尿核苷是膀胱癌识别的潜在生物标志物。
这些结果表明尿核苷可能作为膀胱癌的肿瘤生物标志物有用,且新的生物标志物选择方法是有效的。