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
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Kyung-Hee Kim1,2, Jungnam Joo3, Boram Park3, Sang-Jae Park4, Woo Jin Lee4, Sung-Sik Han4, Tae Hyun Kim4, Eun Kyung Hong4, Sang Myung Woo1,4 and Byong Chul Yoo1
1Biomarker Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea
2Omics Core Laboratory, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea
3Biometrics Research Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea
4Center for Liver Cancer, Hospital, National Cancer Center, Goyang 10408, Republic of Korea
Sang Myung Woo, email: [email protected]
Byong Chul Yoo, email: [email protected]
Keywords: metabolic biomarkers; intrahepatic cholangiocarcinoma
Received: August 30, 2017 Accepted: October 25, 2017 Published: November 22, 2017
We searched for metabolic biomarkers that may predict the prognosis of patients with intrahepatic cholangiocarcinoma (IHCC). To this end, a total of 237 serum samples were obtained from IHCC patients (n = 87) and healthy controls (n = 150), and serum metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two stratified algorithms were used to select the metabolites, the levels of which predicted the prognosis of IHCC patients. We performed MS/MS and multiple-reaction-monitoring MS analyses to identify and quantify the selected metabolites. Continuous biomarker levels were dichotomized based on cutoffs that maximized between-group differences in recurrence-free survival (RFS) in terms of the log-rank test statistic. These RFS differences were analyzed using the log-rank test, and survival curves were drawn with the aid of the Kaplan–Meier method. Six metabolites (l-glutamine, lysophosphatidylcholine [LPC] 16:0, LPC 18:0, N’-methyl-2-pyridone-5-carboxamide [2PY], fibrinopeptide A [FPA] and uric acid) were identified as candidate metabolic biomarkers for predicting the prognosis of IHCC patients. Of these metabolites, levels of l-glutamine, uric acid, LPC 16:0, and LPC 18:0 were significantly lower in the serum from IHCC patients, whereas levels of 2PY and FPA were significantly higher (p < 0.01). 2PY and LPC 16:0 showed significantly better RFS at low level than high level (2PY, median RFS: 15.16 months vs. 5.90 months, p = 0.037; LPC 16:0, median RFS: 15.62 months vs. 9.83 months, p = 0.035). The findings of this study suggest that 2PY and LPC 16:0 identified by metabolome-based approaches may be useful biomarkers for IHCC patients.
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