Xiao Y, Chen Y, Kennedy A W, Belinson J, Xu Y
Department of Cancer Biology, Cleveland Clinic Foundation, Ohio 44195, USA.
Ann N Y Acad Sci. 2000 Apr;905:242-59. doi: 10.1111/j.1749-6632.2000.tb06554.x.
We previously reported that lysophosphatidic acid (LPA) represents a potential biomarker for ovarian and other gynecologic cancers. To further improve the accuracy and potentially increase the sensitivity and specificity of the assay, we developed an electrospray ionization mass spectrometry (ESI-MS)-based method to analyze LPA and related lysophospholipids. LPA, lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS), and lysophosphatidylcholine (LPC) could be detected with high sensitivity (in low pmol range) using this method. Standard curves were established for quantitative analysis. LPA and closely related lysophospholipids isolated from thin-layer chromatography (TLC) plates were analyzed directly by ESI-MS. This ESI-MS-based assay allows simultaneous detection and quantitation of all different species of LPAs and LPIs in a sample over a range of at least 5-300 pmol. Moreover, this test was at least 50 times more sensitive when a multiple reaction monitoring (MRM) mode was used. Using these protocols in a limited set of analysis, we found that both LPA and LPI were elevated in patients with ovarian cancer.
我们之前报道过,溶血磷脂酸(LPA)是卵巢癌和其他妇科癌症的一种潜在生物标志物。为了进一步提高检测的准确性,并有可能提高其灵敏度和特异性,我们开发了一种基于电喷雾电离质谱(ESI-MS)的方法来分析LPA和相关的溶血磷脂。使用该方法能够高灵敏度地检测到LPA、溶血磷脂酰肌醇(LPI)、溶血磷脂酰丝氨酸(LPS)和溶血磷脂酰胆碱(LPC)(低皮摩尔范围)。建立了标准曲线用于定量分析。从薄层色谱(TLC)板上分离出的LPA和密切相关的溶血磷脂直接通过ESI-MS进行分析。这种基于ESI-MS的检测方法能够在至少5 - 300皮摩尔的范围内同时检测和定量样品中所有不同种类的LPA和LPI。此外,当使用多反应监测(MRM)模式时,该检测的灵敏度至少提高了50倍。在一组有限的分析中使用这些方案,我们发现卵巢癌患者的LPA和LPI水平均升高。