title: Differential levels of L-homocysteic acid and lysophosphatidylcholine (16:0) in sera of patients with ovarian cancer.
abstract: Ovarian cancer (OVC) is one of the most difficult types of cancer to detect in the early stages of its development. There have been numerous attempts to identify a biomarker for OVC; however, an accurate diagnostic marker has yet to be identified. The present study profiled OVC candidate metabolites from the serum to identify potential diagnostic markers for OVC. Data regarding low-mass ions (LMIs) in the serum were obtained using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight analysis. MALDI-mass spectrometry (MS) analysis of each serum sample was repeated six times in order to reduce the likelihood of experimental errors. The intensity of the LMI mass peaks were normalized using total peak area sums. The normalized intensity of LMI was used in principal component analysis-discriminant analysis to differentiate between 142 patients with OVC and 100 healthy control participants. Liquid chromatography-MS/MS was used to identify the selected LMIs. Extracted ion chromatogram analysis was used to measure the relative quantity of candidate metabolites from the LMI mass peak areas. The concentration of common metabolites in the serum was determined using ELISA. The top 20 LMI mass peaks with a weigh factor over 0.05 were selected to distinguish between the patients with OVC and the controls. Among the LMIs, two with 184.05 and 496.30 m/z were identified as L-homocysteic acid (HCA) and lysophosphatidylcholine (LPC) (16:0), respectively. The relative quantity of LPC (16:0) was found to be decreased in the OVC serum (P=0.05), while the quantity of HCA was observed to be significantly higher in the OVC serum (P<0.001). HCA was not detected in 59 cases out of the 63 control participants; however, the majority of the cases of OVC (16/25) exhibited significantly higher quantities of HCA. When the cutoff was 10 nmol/ml, the sensitivity and specificity of HCA were 64.0 and 96.9%, respectively. The level of LPC (16:0) was significantly correlated with tumor grade (P=0.045). HCA and LPC (16:0) showed correlation with stage and tumor histology, but the limited sample size resulted in a lack of statistical significance. The findings of the present study suggest that HCA may have potential to be a biomarker for OVC. The stratified screening including LPC (16:0) did not significantly increase the power for OVC screening; however, the present study showed that profiling LMIs in serum may be useful for identifying candidate metabolites for OVC screening.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ewha Woman's University Mokdong Hospital, Ewha Woman's University School of Medicine, Seoul 158-710, Republic of Korea.
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ewha Woman's University Mokdong Hospital, Ewha Woman's University School of Medicine, Seoul 158-710, Republic of Korea.
authors.forename: Yun Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea.
authors.forename: Sun-A
authors.initials: SA
authors.lastname: Ahn
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea.
authors.forename: Kun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea.
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ewha Woman's University Mokdong Hospital, Ewha Woman's University School of Medicine, Seoul 158-710, Republic of Korea.
authors.forename: Jun Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Gyeonggi 440-746, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Colorectal Cancer Branch, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea.
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
keywords: L-homocysteic acid; biomarker; cancer screening; lysophosphatidylcholine (16:0); ovarian cancer