Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Korea.
Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
J Am Soc Mass Spectrom. 2020 Apr 1;31(4):917-926. doi: 10.1021/jasms.9b00102. Epub 2020 Mar 24.
Recently, the parylene-matrix chip was developed for quantitative analysis of small molecules less than 1 kDa. In this study, MALDI-TOF MS based on the parylene-matrix chip was performed to clinically diagnose intrahepatic cholangiocarcinoma (IHCC) and colorectal cancer (CRC). The parylene-matrix chip was applied for the detection of small cancer biomarkers, including -methyl-2-pyridone-5-carboxamide (2PY), glutamine, lysophosphatidylcholine (LPC) 16:0, and LPC 18:0. The feasibility of MALDI-TOF MS based on the parylene-matrix chip was confirmed via analysis of spot-to-spot and shot-to-shot reproducibility. Serum metabolite markers of IHCC, -methyl-2-pyridone-5-carboxamide (2PY), and glutamine were quantified using MALDI-TOF MS based on the parylene-matrix chip. For clinical diagnosis of CRC, two water-insoluble (barely soluble) biomarkers, lysophosphatidylcholine (LPC) 16:0 and LPC 18:0, were quantified. Finally, glutamine and LPC 16:0 were simultaneously detected at a range of concentrations in sera from colon cancer patients using the parylene-matrix chip. Thus, this method yielded high-throughput detection of cancer biomarkers for the mixture samples of water-soluble analytes (2PY and glutamine) and water-insoluble analytes (LPC 16:0 and LPC 18:0).
最近，开发了一种基于对二甲苯基质芯片的方法，用于定量分析小于 1 kDa 的小分子。本研究采用基于对二甲苯基质芯片的 MALDI-TOF MS 对肝内胆管癌 (IHCC) 和结直肠癌 (CRC) 进行临床诊断。该对二甲苯基质芯片用于检测包括 -甲基-2-吡啶酮-5-甲酰胺 (2PY)、谷氨酰胺、溶血磷脂酰胆碱 (LPC) 16:0 和 LPC 18:0 在内的小癌症生物标志物。通过斑点间和射间重现性分析，证实了基于对二甲苯基质芯片的 MALDI-TOF MS 的可行性。采用基于对二甲苯基质芯片的 MALDI-TOF MS 对 IHCC 的血清代谢标志物 -甲基-2-吡啶酮-5-甲酰胺 (2PY) 和谷氨酰胺进行定量分析。为了对 CRC 进行临床诊断，对两种不溶 (几乎不溶) 的生物标志物溶血磷脂酰胆碱 (LPC) 16:0 和 LPC 18:0 进行定量分析。最后，使用对二甲苯基质芯片同时检测结肠癌患者血清中 LPC 16:0 和谷氨酰胺在一系列浓度下的浓度。因此，该方法可对水溶性分析物 (2PY 和谷氨酰胺) 和水不溶性分析物 (LPC 16:0 和 LPC 18:0) 的混合物样品进行高通量的癌症生物标志物检测。
