Department of Biochemistry and Molecular Biology, PC Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Int J Cancer. 2013 Dec 1;133(11):2662-71. doi: 10.1002/ijc.28285. Epub 2013 Jul 1.
Mass spectrometry (MS) has the unique ability to profile, in an easily accessible body tissue (peripheral blood/serum,) the sizes and relative amounts of a wide variety of biomolecules in a single platform setting. Using electrospray ionization (ESI)-MS, we distinguished individual serum from wild-type control mice from serum of mice containing an oncogenic Kras mutation, which leads to development of pancreatic ductal adenocarcinoma (PDAC) similar to that observed in humans. Identification of differences in significant ESI-MS sera mass peaks between Kras-activated mice and control mice was performed using t tests and a "nested leave one out" cross-validation procedure. Peak distributions in serum of control mice from mice with Kras-mutant-dependent PDAC were distinguished from those of pancreatic intraepithelial neoplasia (PanIN) lesions (p = 0.00024). In addition, Kras mutant mice with PDAC were distinguished from Kras mutant mice with PanIN alone (p = 0.0057). Test specificity, a measure of the false positives, was greater for the control vs. Kras mutated mice, and the test sensitivity, a measure of false negatives, was greater for the PDAC vs. PanIN containing mice. Receiver-operating characteristic (ROC) curve discriminatory values were 0.85 for both comparisons. These studies indicate ESI-MS serum mass profiling can detect physiological changes associated with pancreatic cancer initiation and development in a GEM (genetic engineered mouse) model that mimics pancreatic cancer development in humans. Such technology has the potential to aid in early detection of pancreatic cancer and in developing therapeutic drug interventions.
质谱（MS）具有独特的能力，可在单个平台设置中，轻松地对各种生物分子的大小和相对含量进行分析。使用电喷雾电离（ESI）-MS，我们可以区分来自野生型对照小鼠的血清与含有致癌性 Kras 突变的小鼠的血清，该突变导致类似于人类观察到的胰腺导管腺癌（PDAC）的发展。使用 t 检验和“嵌套留一交叉验证”程序，对 Kras 激活小鼠和对照小鼠的 ESI-MS 血清质量峰之间的差异进行鉴定。来自具有 Kras 突变依赖性 PDAC 的小鼠的血清中的峰分布与胰腺上皮内瘤变（PanIN）病变区分开（p = 0.00024）。此外，具有 PDAC 的 Kras 突变小鼠与仅具有 PanIN 的 Kras 突变小鼠区分开（p = 0.0057）。对照与 Kras 突变小鼠相比，测试特异性（假阳性的度量）更高，而 PDAC 与含有 PanIN 的小鼠相比，测试灵敏度（假阴性的度量）更高。这两种比较的接收者操作特征（ROC）曲线鉴别值均为 0.85。这些研究表明，ESI-MS 血清质量分析可以在模拟人类胰腺癌发展的 GEM（遗传工程小鼠）模型中检测与胰腺癌起始和发展相关的生理变化。这种技术有可能有助于早期发现胰腺癌和开发治疗性药物干预措施。
