Metabolomics identifies serum and exosomes metabolite markers of pancreatic cancer

Tao, Lianyuan; Zhou, Juntuo; Yuan, Chunhui; Zhang, Lingfu; Li, Deyu; Si, Dandan; Xiu, Dianrong; Zhong, Lijun

doi:10.1007/s11306-019-1550-1

Original Article
Published: 30 May 2019

Metabolomics identifies serum and exosomes metabolite markers of pancreatic cancer

Lianyuan Tao^1,2^na1,
Juntuo Zhou³^na1,
Chunhui Yuan²,
Lingfu Zhang²,
Deyu Li¹,
Dandan Si⁵,
Dianrong Xiu² &
Lijun Zhong ORCID: orcid.org/0000-0002-4228-182X⁴

Metabolomics volume 15, Article number: 86 (2019) Cite this article

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Abstract

Introduction

Pancreatic cancer (PC) is one of the most aggressive malignancies, and it’s difficult to diagnosis PC at an early stage, which leads to the poor prognosis of PC.

Objectives

To identifiy the possible prognosis or dignosis metabolite biomarkers in the serum exosome of PC patients.

Methods

We employed LC-DDA-MS based untargeted lipidomic analysis to search for potential candidate biomarkers in the serum exosome of PC patients. Then LC-MRM-MS based targeted lipid quantification was used to validate the trends of the candidate biomarkers in larger sample cohorts.

Results

About 270 lipids belonging to 20 lipid species were found significantly dysregulated between the serum exosome of PC patients and healthy controls. 61 of them were validated in larger samples size. We further analysis the correlation between these dysregulated lipids and other PC related factors, and results show that LysoPC 22:0, PC (P-14:0/22:2) and PE (16:0/18:1) are all associated with tumor stage, CA19-9, CA242 and tumor diameter. What’s more, PE (16:0/18:1) is also found to be significantly correlated with the patient’s overall survival.

Conclusion

These data reveal dysregulated lipids in serum exosome of PC patients, which have potential to be biomarkers for diagnosis, or unveil pathological relationship between exosome and PC progress.

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Abbreviations

PC:: Pancreatic cancer
LC–MS:: Liquid chromatography–mass spectrometry
MS/MS:: Tandem mass spectrometry
Q:: Quadrupole
TOF:: Time of flight
QC:: Quality control
CE:: Cholesteryl ester
Cer:: Ceramide
DG:: Diacylglycerol
FFA:: Free fatty acid
LysoPC:: Lysophosphatidylcholine
LPE:: Lysophosphatidylethanolamine
PC:: Phosphatidylcholine
PE:: Phosphatidylethanolamine
PI:: Phosphatidylinositol
SM:: Sphingomyelin
TG:: Triacylglycerol

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Acknowledgements

This study was supported by a grant from the National Natural Science Foundation of China (No. 81672862), the Capital Characteristic Clinical Application Research and Achievement Promotion Project (No. Z171100001017121), the Doctoral Venture Capital fund of Henan Provincial People’s Hospital (No. ZC20180077),the Special Project of Henan Provincial Key Research, Development and Promotion (Science and Technology) (No. 192102310119), and the Fund for Fostering Young Scholars of Peking University Health Science Center (Grant No. BMU2018PY006).

Author information

Lianyuan Tao and Juntuo Zhou contribute equally to this study.

Affiliations

Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, 450003, Henan, China
Lianyuan Tao & Deyu Li
Department of General Surgery, Peking University Third Hospital, No. 49, Hua Yuan North Rd, Hai Dian District, Beijing, 100191, China
Lianyuan Tao, Chunhui Yuan, Lingfu Zhang & Dianrong Xiu
Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, 100083, China
Juntuo Zhou
Medical and Health Analytical Center, Peking University Health Science Center, Beijing, 100191, China
Lijun Zhong
AB Sciex Analytical Instrument Trading Co., Ltd. Beijing Office, Beijing, 100015, China
Dandan Si

Authors

Lianyuan Tao
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Juntuo Zhou
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Chunhui Yuan
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Lingfu Zhang
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Deyu Li
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Dandan Si
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Dianrong Xiu
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Lijun Zhong
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Contributions

# Dr. Tao Lianyuanand Dr. Zhou Juntuo contribute equally to this study. Tao lianyuan, Zhou Juntuo, XiuDianrong and ZhongLijun conceived and designed this study; Tao Lianyuan and Zhou Juntuo performed exosomes isolation and proteomic identification; Tao Lianyuan, Zhou Juntuo, Li Deyu, XiuDianrong and ZhongLijun performed the analysis and interpretation of data; Tao lianyuan, Yuan Chunhui and Zhang Lingfu performed clinical data collection and samples collection; Tao Lianyuan, Zhou Juntuo, XiuDianrong and ZhongLijun wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Dianrong Xiu or Lijun Zhong.

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The authors declare no conflict of interest.

Ethical approval

This study was approved by the Clinical Ethics Committee of Peking University Third Hospital.

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Cite this article

Tao, L., Zhou, J., Yuan, C. et al. Metabolomics identifies serum and exosomes metabolite markers of pancreatic cancer. Metabolomics 15, 86 (2019). https://doi.org/10.1007/s11306-019-1550-1

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Received: 29 January 2019
Accepted: 24 May 2019
Published: 30 May 2019
DOI: https://doi.org/10.1007/s11306-019-1550-1

Keywords

Pancreatic cancer
Serum exosome
Lipidomics
Exosome biomarker