title: Global and targeted metabolomics of esophageal squamous cell carcinoma discovers potential diagnostic and therapeutic biomarkers.
abstract: Diagnostic and therapeutic biomarkers useful for esophageal squamous cell carcinoma (ESCC) have the ability to increase the long term survival of cancer patients. A metabolomics study, using plasma from four groups including ESCC patients before, during, and after chemoradiotherapy (CRT) and healthy controls, was originally carried out by LC-MS to determine global alterations in the metabolic profiles and find biomarkers potentially applicable to diagnosis and monitoring treatment effects. It is worth pointing out that a clear clustering and separation of metabolic data from the four groups was observed, which indicated that disease status and treatment intervention resulted in specific metabolic perturbations in the patients. A series of metabolites were found to be significantly altered in ESCC patients versus healthy controls and in pre- versus post-treatment patients based on multivariate statistical data analysis (MVDA). To further validate the reliability of these potential biomarkers, an independent validation was performed by using the selected reaction monitoring (SRM) based targeted approach. Finally, 18 most significantly altered plasma metabolites in ESCC patients, relative to healthy controls, were tentatively identified as lysophosphatidylcholines (lysoPCs), fatty acids, l-carnitine, acylcarnitines, organic acids, and a sterol metabolite. The classification performance of these metabolites were analyzed by receiver operating characteristic (ROC)(1) analysis and a biomarker panel was generated. Together, biological significance of these metabolites was discussed. Comparison between pre- and post-treatment patients generated 11 metabolites as potential therapeutic biomarkers that were tentatively identified as amino acids, acylcarnitines, and lysoPCs. Levels of three of these (octanoylcarnitine, lysoPC(16:1), and decanoylcarnitine) were closely correlated with treatment effect. Moreover, variation of these three potential biomarkers was investigated over the treatment course. The results suggest that these biomarkers may be useful in diagnosis, as well as in monitoring therapeutic responses and predicting outcomes of the ESCC.
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
authors: Jing
authors: J
authors: Xu
authors: Yanhua
authors: Y
authors: Chen
authors: Ruiping
authors: R
authors: Zhang
authors: Yongmei
authors: Y
authors: Song
authors: Jianzhong
authors: J
authors: Cao
authors: Nan
authors: N
authors: Bi
authors: Jingbo
authors: J
authors: Wang
authors: Jiuming
authors: J
authors: He
authors: Jinfa
authors: J
authors: Bai
authors: Lijia
authors: L
authors: Dong
authors: Luhua
authors: L
authors: Wang
authors: Qimin
authors: Q
authors: Zhan
authors: Zeper
authors: Z
authors: Abliz
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D002331:Carnitine / Q000097:blood; D016022:Case-Control Studies; D059248:Chemoradiotherapy; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D008244:Lysophosphatidylcholines / Q000097:blood; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D015999:Multivariate Analysis; D012372:ROC Curve; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D008244:Lysophosphatidylcholines; D002331:Carnitine
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