Martorella Andrew, Robbins Richard
Department of Medicine, Endocrinology Service, Memorial Sloan-Kettering Cancer Center, New York, USA.
Acta Biomed. 2007;78 Suppl 1:123-8.
Recent advances in mass spectrometry have enabled the identification of hundreds of low molecular weight (LMW) peptides that have previously been difficult to detect in human serum. Serum peptide patterns can now be analyzed using commercially available statistical programs to identify potential peptide patterns that may correlate with the presence or absence of specific diseases. A serum peptide profile (SPP), which is unique to each patient, can be created and compared to a known SPP from a specific disease. The SPP thus serves as a potential early stage biomarker prior to the clinical manifestation of disease. A unique and automated technology platform has been developed by members of the Protein Center at Memorial Sloan-Kettering Cancer Center (MSKCC). It involves a magnetic bead-based approach to extract LMW peptides from serum, placing them by robotic automation on a stainless steel MALDI-TOF target plate, subjecting them to mass spectrometric analysis, and using GeneSpring software to analyze the peptide patterns. Human serum from a cohort of 27 patients with metastatic thyroid cancer and 32 controls were analyzed on the MSKCC platform. 549 individual LMW peptides were identified. A SPP composed of 98 discriminatory LMW peptides was able to distinguish between the two groups of serum samples with high statistical accuracy. We believe that our automated system will serve as a model for future biotechnology laboratories in the quest for hidden diagnostic clues that may be detected by simply analyzing a drop of blood.
质谱分析技术的最新进展使得人们能够鉴定出数百种低分子量（LMW）肽，而这些肽此前在人血清中很难检测到。现在可以使用市售的统计程序来分析血清肽谱，以识别可能与特定疾病的存在与否相关的潜在肽谱。可以创建每个患者独有的血清肽谱（SPP），并与特定疾病的已知SPP进行比较。因此，SPP可作为疾病临床表现出现之前的潜在早期生物标志物。纪念斯隆凯特琳癌症中心（MSKCC）蛋白质中心的成员开发了一个独特的自动化技术平台。它采用基于磁珠的方法从血清中提取LMW肽，通过机器人自动化将它们放置在不锈钢基质辅助激光解吸电离飞行时间（MALDI-TOF）靶板上，对其进行质谱分析，并使用GeneSpring软件分析肽谱。在MSKCC平台上分析了来自27名转移性甲状腺癌患者和32名对照的人血清。鉴定出549种个体LMW肽。由98种具有鉴别性的LMW肽组成的SPP能够以高统计准确性区分两组血清样本。我们相信，我们的自动化系统将成为未来生物技术实验室的一个模型，用于寻找可能通过简单分析一滴血就能检测到的隐藏诊断线索。
