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.

Low-mass-ion discriminant equation (LOME) for ovarian cancer screening

“…If lysophospholipids were released to the bloodstream, they might serve as cancer screening markers. Among lysophospholipids, LPC 16:0 has been reported as a potential biomarker not only for OVC but also for other types of cancer [ 19 ], and our previous and present studies confirmed its potential screening power for OVC [ 9 ] (Figs. 6 and 8 ).…”

“…Many studies have shown increased rates of glycolysis, glutaminolysis, and lipid synthesis in cancers, suggesting that altered metabolism promotes tumor growth [ 8 ]. Metabolomics has been utilized to identify novel biomarkers that could be used to distinguish cancer patients from their counterparts without neoplasms [ 6 , 7 , 9 – 11 ]. Exploring metabolic signatures of biological specimens would aid in the early diagnosis of ovarian cancer and also clarification of disease pathogenesis.…”

Reduced levels of N’-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine 16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the correlation with recurrence-free survival

“…The metabolic ion of (negative) 167.0211 m/z with an RT of 2.48 min was shown to have originated from uric acid (HMDB00289) (Figure 4 ). Two other metabolic ions (of 496.3398 m/z with an RT of 14.977 min and 768.8499 m/z with an RT 7.544 min) had been identified as LPC 16:0 [ 12 ] and fibrinopeptide A [ 9 ], respectively, in our previous studies.…”

“…Similar to LPA and ATX, reduced LPC levels have been reported in the blood and tissue samples of patients with many types of cancer (serum from ovarian cancer patients [ 12 ]; and tissues from gastric [ 31 ], prostate [ 32 ], and liver [ 33 ] cancer patients). Higher LPC 18:0 plasma levels were associated with lower risks of breast, prostate, and colorectal cancers [ 34 ].…”

Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study

“…The lower levels of LysoPCs may reflect a higher metabolism rate in cancer patients. LysoPC is an important intermediate in the degradation and biosynthesis of phosphatidylcholine (PC) which has been an important biomarker in cancer diagnosis, such as breast cancer22, lung cancer23, ovarian cancer2425, gastric cancer26, colorectal cancer27 and melanoma28. LysoPC levels were shown to be decreased in the serum or urine of these cancer patients.…”