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Metabolomics

, 12:116 | Cite as

Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS

  • Jialin Wang
  • Tao Zhang
  • Xiaotao Shen
  • Jia Liu
  • Deli Zhao
  • Yawen Sun
  • Lu Wang
  • Yingjun Liu
  • Xiaoyun Gong
  • Yanxun Liu
  • Zheng-Jiang Zhu
  • Fuzhong Xue
Original Article

Abstract

Introduction

Previous metabolomics studies have revealed perturbed metabolic signatures in esophageal squamous cell carcinoma (ESCC) patients, however, most of these studies included mainly late-staged ESCC patients due to the difficulties of collecting the early-staged samples from asymptotic ESCC subjects.

Objectives

This study aims to explore the early-staged ESCC metabolic signatures and potential of serum metabolomics to diagnose ESCC at early stages.

Methods

Serum samples of 97 ESCC patients (stage 0, 39 cases; stage I, 17 cases; stage II, 11 cases, stage III, 30 cases) and 105 healthy controls (HC) were enrolled and randomly separated into training data (77 ESCCs, 84 HCs) and validation data (20 ESCCs, 21 HCs). Untargeted metabolomics was performed to identify ESCC-related metabolic signatures.

Results

The global metabolomics profiles could clearly distinguish ESCC from HC in training data. 16 ascertained metabolites were found to be disturbed in the metabolic pathways characterized by dysregulated fatty acid biosynthesis, glycerophospholipid metabolism, choline metabolism in cancer and linoleic acid metabolism. The AUC value in validation data was 0.895, with sensitivity 85.0 % and specificity 90.5 %. Good diagnostic performances were also achieved for early stage ESCC, with the values of area under the curve (AUC) 0.881 for the ESCC patients in both stage 0 and I–II. In addition, six metabolites were found to discriminate ESCC stages. Among them, three biomarkers, dodecanoic acid, LysoPA(18:1), and LysoPC(14:0), exhibited clear trend for ESCC progression.

Conclusion

These findings suggest serum metabolomics, performed in a minimally noninvasive and convenient manner, may possess great potential for early diagnosis of ESCC patients.

Keywords

Esophageal squamous cell carcinoma Metabolomics Early diagnosis UHPLC-QTOF/MS Biomarker 

Notes

Acknowledgments

This work was funded by National Natural Science Foundation of China (Grant Number 81573246, 81302514, 81573259, 21575151), Science and Technology Research Projects of Shandong Province (2014GSF118022), and National Natural Science Foundation of Shandong Province (RZ2014HP044). Z.-J. Z. is supported by Thousand Youth Talents Program from Chinese government and Agilent Technologies Thought Leader Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Human and animal rights

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11306_2016_1050_MOESM1_ESM.docx (2.2 mb)
Supplementary material 1 (DOCX 2207 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jialin Wang
    • 1
    • 4
  • Tao Zhang
    • 2
  • Xiaotao Shen
    • 3
  • Jia Liu
    • 2
    • 5
  • Deli Zhao
    • 6
  • Yawen Sun
    • 1
    • 4
  • Lu Wang
    • 2
  • Yingjun Liu
    • 2
  • Xiaoyun Gong
    • 2
  • Yanxun Liu
    • 2
  • Zheng-Jiang Zhu
    • 3
  • Fuzhong Xue
    • 2
  1. 1.The Shandong Cancer Hospital Affiliated to Shandong UniversityJinanChina
  2. 2.Department of Epidemiology and Biostatistics, School of Public HealthShandong UniversityJinanChina
  3. 3.Interdisciplinary Research Center on Biology and Chemistry, and Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiChina
  4. 4.Shandong Cancer Hospital and InstituteShandong Academy of Medical SciencesJinanChina
  5. 5.Yanjing Medical CollegeCapital Medical UniversityBeijingChina
  6. 6.Tumor Preventative and Therapeutic Base of Shandong ProvinceFeicheng People’s HospitalFeichengChina

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