使用基质辅助激光解吸电离质谱分析鉴定胆管癌潜在的血清肽生物标志物
Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling.
作者信息
Sandanayake Neomal S, Camuzeaux Stephane, Sinclair John, Blyuss Oleg, Andreola Fausto, Chapman Michael H, Webster George J, Smith Ross C, Timms John F, Pereira Stephen P
机构信息
UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London, London, UK.
Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, London, UK.
出版信息
BMC Clin Pathol. 2014 Feb 4;14(1):7. doi: 10.1186/1472-6890-14-7.
BACKGROUND
The aim of this discovery study was the identification of peptide serum biomarkers for detecting biliary tract cancer (BTC) using samples from healthy volunteers and benign cases of biliary disease as control groups. This work was based on the hypothesis that cancer-specific exopeptidases exist and that their activities in serum can generate cancer-predictive peptide fragments from circulating proteins during coagulation.
METHODS
This case control study used a semi-automated platform incorporating polypeptide extraction linked to matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) to profile 92 patient serum samples. Predictive models were generated to test a validation serum set from BTC cases and healthy volunteers.
RESULTS
Several peptide peaks were found that could significantly differentiate BTC patients from healthy controls and benign biliary disease. A predictive model resulted in a sensitivity of 100% and a specificity of 93.8% in detecting BTC in the validation set, whilst another model gave a sensitivity of 79.5% and a specificity of 83.9% in discriminating BTC from benign biliary disease samples in the training set. Discriminatory peaks were identified by tandem MS as fragments of abundant clotting proteins.
CONCLUSIONS
Serum MALDI MS peptide signatures can accurately discriminate patients with BTC from healthy volunteers.
背景
这项探索性研究的目的是利用健康志愿者和胆道疾病良性病例的样本作为对照组，鉴定用于检测胆道癌（BTC）的肽类血清生物标志物。这项工作基于这样的假设，即存在癌症特异性外肽酶，并且它们在血清中的活性可在凝血过程中从循环蛋白产生癌症预测性肽片段。
方法
这项病例对照研究使用了一个半自动平台，该平台结合了与基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）相连的多肽提取技术，对92份患者血清样本进行分析。生成预测模型以测试来自BTC病例和健康志愿者的验证血清组。
结果
发现了几个肽峰，它们可以显著区分BTC患者与健康对照和良性胆道疾病患者。一个预测模型在验证组中检测BTC的灵敏度为100%，特异性为93.8%，而另一个模型在训练组中区分BTC与良性胆道疾病样本的灵敏度为79.5%，特异性为83.9%。串联质谱鉴定出具有鉴别力的峰为丰富凝血蛋白的片段。
结论
血清MALDI MS肽谱可以准确区分BTC患者与健康志愿者。
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