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

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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.

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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.

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    Authors and Affiliations

    1. The Shandong Cancer Hospital Affiliated to Shandong University, Jinan, 250117, China

      Jialin Wang & Yawen Sun

    2. Department of Epidemiology and Biostatistics, School of Public Health, Shandong University, PO Box 100, Jinan, 250012, China

      Tao Zhang, Jia Liu, Lu Wang, Yingjun Liu, Xiaoyun Gong, Yanxun Liu & Fuzhong Xue

    3. Interdisciplinary Research Center on Biology and Chemistry, and Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China

      Xiaotao Shen & Zheng-Jiang Zhu

    4. Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, 250117, China

      Jialin Wang & Yawen Sun

    5. Yanjing Medical College, Capital Medical University, Beijing, 101300, China

      Jia Liu

    6. Tumor Preventative and Therapeutic Base of Shandong Province, Feicheng People’s Hospital, Feicheng, 271600, China

      Deli Zhao

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    1. Jialin Wang
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    Correspondence to Jialin Wang, Zheng-Jiang Zhu or Fuzhong Xue.

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    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.

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    Fuzhong Xue is the primary corresponding author.

    J. Wang, T. Zhang and X. Shen made equally contributions.

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    Wang, J., Zhang, T., Shen, X. et al. Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS. Metabolomics 12, 116 (2016). https://doi.org/10.1007/s11306-016-1050-5

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