Hara Tomohiko, Honda Kazufumi, Ono Masaya, Naito Katsusuke, Hirohashi Setsuo, Yamada Tesshi
Chemotherapy Division and Cancer Proteomics Project, National Cancer Center Research Institute, Tsukiji, Tokyo, Japan.
J Urol. 2005 Oct;174(4 Pt 1):1213-7. doi: 10.1097/01.ju.0000173915.83164.87.
Surface enhanced laser desorption/ionization mass spectrometry can generate robust information from a small amount of clinical samples such as serum and plasma. In this study we identified novel diagnostic biomarkers of renal cell carcinoma (RCC) by large-scale serum protein profiling using surface enhanced laser desorption/ionization mass spectrometry.
Proteomic spectra were generated by a time of flight mass spectrometer from a set of training samples (21 patients with RCC and 24 healthy volunteers) and another set of validation samples (19 patients with RCC, 20 healthy volunteers and 5 patients with pyelonephritis). Information on the peaks (intensity and m/z) was extracted from the mass spectra using newly developed algorithms, and the Mann-Whitney's U test and linear support vector machine were used to identify the peaks distinguishing RCC samples from the controls.
Two peaks with molecular masses of 4,151 and 8,968 m/z were selected as significantly more prominent in RCC samples (p <0.01) among the 3,539 peaks in the range of 3,000 to 30,000 m/z obtained from the training samples. Simultaneous recognition of these 2 biomarkers was shown to have a sensitivity of 89.5% for the diagnosis of RCC and an overall specificity of 80.0% (95% [19 of 20] of healthy volunteers and 20% [1 of 5] of patients with pyelonephritis) in the blinded validation samples, and to allow detection of RCC in stage I (UICC) in 88.9% (16 of 18) of the cases.
We identified 2 serum biomarkers potentially useful for the early diagnosis of RCC. This finding warrants a further large-scale multi-institutional analysis for clinical evaluation of the diagnostic significance of these biomarkers.
表面增强激光解吸/电离质谱法能够从少量临床样本（如血清和血浆）中获取丰富信息。在本研究中，我们通过表面增强激光解吸/电离质谱法进行大规模血清蛋白谱分析，以鉴定肾细胞癌（RCC）的新型诊断生物标志物。
采用飞行时间质谱仪从一组训练样本（21例RCC患者和24名健康志愿者）以及另一组验证样本（19例RCC患者、20名健康志愿者和5例肾盂肾炎患者）中生成蛋白质组谱。使用新开发的算法从质谱中提取峰信息（强度和质荷比），并采用曼-惠特尼U检验和线性支持向量机来识别区分RCC样本与对照的峰。
在从训练样本获得的3000至30000 m/z范围内的3539个峰中，选择分子量为4151和8968 m/z的两个峰，其在RCC样本中明显更为突出（p <0.01）。在盲法验证样本中，同时识别这两种生物标志物对RCC诊断的敏感性为89.5%，总体特异性为80.0%（20名健康志愿者中的95% [19/20]和5例肾盂肾炎患者中的20% [1/5]），并且能够在88.9%（16/18）的病例中检测出I期（国际抗癌联盟）RCC。
我们鉴定出两种可能对RCC早期诊断有用的血清生物标志物。这一发现需要进一步进行大规模多机构分析，以临床评估这些生物标志物的诊断意义。
