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).
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# 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.
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This study was approved by the Clinical Ethics Committee of Peking University Third Hospital.
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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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DOI: https://doi.org/10.1007/s11306-019-1550-1