Biomarker Branch, Research Institute, National Cancer Center, Goyang, Korea.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
Cancer Res Treat. 2018 Jul;50(3):883-893. doi: 10.4143/crt.2017.275. Epub 2017 Sep 18.
We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers.
A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening.
Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine.
MALDI-TOF-based OVC LOMEs combined with triple-TOF-based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.
我们旨在开发基质辅助激光解吸电离飞行时间（MALDI-TOF）基础的卵巢癌（OVC）低质量离子判别方程（LOME），并评估三重飞行时间质谱分析在识别代谢生物标志物方面可能的支持作用。
对 114 例 OVC 患者和良性卵巢肿瘤患者的血清样本进行 MALDI-TOF 分析，对 137 例健康女性个体及 OVC、结直肠癌、肝胆癌和胰腺癌患者的血清样本进行三重飞行时间质谱分析。通过参考判别性低质量离子（LMI）对的峰强度比构建 OVC LOME。三重飞行时间质谱分析用于筛选和鉴定 OVC 筛查的代谢生物标志物。
最终使用判别性 LMI 对（137.1690 和 84.4119 m/z；496.5022 和 709.7642 m/z；和 524.5614 和 709.7642 m/z）构建了三个 OVC LOME，均具有>90%的准确性。496.5022 m/z 和 524.5614 m/z 的 LMI 是溶血磷脂酰胆碱（LPC）16：0 和 LPC 18：0 的 LMI。三重飞行时间质谱分析选择了 7 个有区别的 LMI；每个 LMI 的特异性>90%。在 OVC 患者的血清中，有 7 个 LMI 中的 4 个（在保留时间 2.04-3.14 分钟处具有 137.0455 m/z 离子）上调，该离子被鉴定为来自次黄嘌呤的离子。
基于 MALDI-TOF 的 OVC LOME 与基于三重飞行时间质谱的 OVC 代谢生物标志物相结合，可实现可靠的 OVC 筛查；两种技术在定量和定性上相互补充。
