, 14:109 | Cite as

A systematic review on metabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer

  • Nguyen Phuoc Long
  • Sang Jun Yoon
  • Nguyen Hoang Anh
  • Tran Diem Nghi
  • Dong Kyu Lim
  • Yu Jin Hong
  • Soon-Sun Hong
  • Sung Won Kwon
Review Article



Metabolomics is an emerging approach for early detection of cancer. Along with the development of metabolomics, high-throughput technologies and statistical learning, the integration of multiple biomarkers has significantly improved clinical diagnosis and management for patients.


In this study, we conducted a systematic review to examine recent advancements in the oncometabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer.


PubMed, Scopus, and Web of Science were searched for relevant studies published before September 2017. We examined the study designs, the metabolomics approaches, and the reporting methodological quality following PRISMA statement.

Results and Conclusion

The included 25 studies primarily focused on the identification rather than the validation of predictive capacity of potential biomarkers. The sample size ranged from 10 to 8760. External validation of the biomarker panels was observed in nine studies. The diagnostic area under the curve ranged from 0.68 to 1.00 (sensitivity: 0.43–1.00, specificity: 0.73–1.00). The effects of patients’ bio-parameters on metabolome alterations in a context-dependent manner have not been thoroughly elucidated. The most reported candidates were glutamic acid and histidine in seven studies, and glutamine and isoleucine in five studies, leading to the predominant enrichment of amino acid-related pathways. Notably, 46 metabolites were estimated in at least two studies. Specific challenges and potential pitfalls to provide better insights into future research directions were thoroughly discussed. Our investigation suggests that metabolomics is a robust approach that will improve the diagnostic assessment of pancreatic cancer. Further studies are warranted to validate their validity in multi-clinical settings.


Pancreatic cancer Metabolomics Diagnostic biomarkers Systematic review 



Area under the curve


Branched-chain amino acids


Chronic pancreatitis


Gas chromatography–mass spectrometry


Liquid chromatography–mass spectrometry


Magnetic resonance imaging


Tandem mass spectrometry


Nuclear magnetic resonance


Orthogonal projections to latent structures discriminant analysis


Pancreatic cancer


Principal component analysis


Pancreatic ductal adenocarcinoma


Partial least squares discriminant analysis


Partial least squares discriminant function


Cross-validated coefficient of determination


Coefficient of determination


Receiver operating characteristic curve


Supercritical fluid extraction-supercritical fluid chromatography coupled with tandem mass spectrometry


Author contributions

SWK and SSH supervised the project. SWK, SSH, and NPL contributed to the study design. NPL, SJY, NHA, TDN, DKL, and YJH searched and collected the data. NPL, SJY, NHA, TDN, DKL, and YJH performed data processing and interpretation. NPL, SJY, NHA, and TDN prepared the first draft of the manuscript. All authors have read, revised critically, and approved the final manuscript.


The Bio-Synergy Research Project of the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (NRF-2012M3A9C4048796), the National Research Foundation of Korea (NRF-2017R1E1A2A02022658, NRF-2018R1A5A2024425), and the BK21 Plus Program in 2017.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

11306_2018_1404_MOESM1_ESM.pdf (1.2 mb)
Supplementary material 1 (PDF 1275 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nguyen Phuoc Long
    • 1
  • Sang Jun Yoon
    • 1
  • Nguyen Hoang Anh
    • 1
  • Tran Diem Nghi
    • 2
  • Dong Kyu Lim
    • 1
  • Yu Jin Hong
    • 1
  • Soon-Sun Hong
    • 3
  • Sung Won Kwon
    • 1
  1. 1.Research Institute of Pharmaceutical Sciences and College of PharmacySeoul National UniversitySeoulSouth Korea
  2. 2.School of MedicineVietnam National UniversityHo Chi Minh CityVietnam
  3. 3.Department of Drug Development, College of MedicineInha UniversityIncheonSouth Korea

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