Profiling of serum metabolites using maldi-tof and triple-tof mass spectrometry to develop a screen for ovarian cancer

Abstract

Purpose We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDITOF)- 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. Materials and Methods 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 analysis was used to select and identify metabolic biomarkers for OVC screening. Results 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, four with a 137.0455 m/z ion at retention times of 2.04-3.14 minutes were upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine. Conclusion 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.