Abstract

Abstract Ovarian cancer (OVC) is one of the most difficult cancers to detection in the early periods of its development. Therefore there have been numerous attempts to find a biomarker for OVC, but an accurate diagnostic marker is yet to be discovered. In this study, we profiled OVC candidate metabolites from serum to find potential diagnostic marker for OVC. Information of low-mass-ions (LMIs) in serum was obtained by using MALDI-TOF. MALDI-MS analysis of each serum sample was repeated six times in order to reduce experimental errors. Intensity of LMI mass peak was normalized using total peak area sums. Normalized intensity of LMI was used in principal component analysis-discriminant analysis (PCA-DA) to discriminate 142 OVC from 100 controls. LC-MS/MS was used to identify the selected LMIs. Extracted ion chromatogram (EIC) analysis was used to measure the relative quantity of candidate metabolite from the LMI mass peak areas. The concentration of common metabolite in serum was determined by ELISA. Top 20 LMI mass peaks with weigh factor over 0.05 were selected to separate OVC from controls. Among them two LMIs with 184.05 m/z and 496.30 m/z were identified as L-homocysteic acid (HCA) and lysophosphatidylcholine (LPC) (16:0), respectively. Relative quantity of LPC (16:0) was decreased in OVC serum (P=0.05), whereas the amount of HCA was significantly higher in OVC serum (P<0.001). HCA was not detected in 59 cases out of 63 controls, but most cases of OVC (16 out of 25) showed significantly higher amount of HCA. When the cutoff was 10 nmol/ml, sensitivity and specificity of HCA were 64.0% and 96.9%, respectively. Level of LPC (16:0) was significantly correlated with tumor grade (P=0.045). Both HCA and LPC (16:0) showed correlation with stage and tumor histology, but limited sample number could not assign the statistical significance. HCA alone showed a potential power of biomarker for OVC. Even the stratified screening including LPC (16:0) did not significantly increase the power for OVC screening, our present study showed that a good example of profiling of LMIs in serum can be useful to select and identify candidate metabolites for OVC screening. Citation Format: Yun Hwan Kim, Woong Ju, Seung Cheol Kim, Byong Chul Yoo. Differential level of L-homocysteic acid and lysophosphatidylcholine (16:0) in sera of patients with ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3478. doi:10.1158/1538-7445.AM2014-3478

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