Abstract
Introduction
Monitoring metabolic biomarkers could be utilized as an effective tool for the early detection of gastric cancer (GC) risk.
Objective
We aimed to discover predictive serum biomarkers for GC and investigate biomarker-related metabolism.
Methods
Subjects were randomly selected from the Korean Cancer Prevention Study-II cohort and matched by age and sex. We analyzed baseline serum samples of 160 subjects (discovery set; control and GC occurrence group, 80 each) via nontargeted screening. Identified putative biomarkers were validated in baseline serum samples of 140 subjects (validation set; control and GC occurrence group, 70 each) using targeted metabolites analysis.
Results
The final analysis was conducted on the discovery set (control, n = 52 vs. GC occurrence, n = 50) and the validation set (control, n = 43 vs. GC occurrence, n = 44) applying exclusion conditions. Eighteen putative metabolite sets differed between two groups found on nontargeted metabolic screening. We focused on fatty acid-related energy metabolism. In targeted analysis, levels of decanoyl-l-carnitine (p = 0.019), l-carnitine (p = 0.033), and citric acid (p = 0.025) were significantly lower in the GC occurrence group, even after adjusting for age, sex, and smoking status. Additionally, l-carnitine and citric acid were confirmed to have an independently significant relationship to GC development. Notably, alkaline phosphatase showed a significant correlation with these two biomarkers.
Conclusion
Changes in serum l-carnitine and citric acid levels that may result from alterations of fatty-acid-related energy metabolism are expected to be valuable biomarkers for the early diagnosis of GC risk.
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Data availability
Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Abbreviations
- ACLY:
-
ATP-citric acid lyase
- ACS:
-
Acyl-CoA synthetases
- ACSL:
-
Long-chain acyl-CoA synthetases
- ALP:
-
Alkaline phosphatase
- BMI:
-
Body mass index
- CI:
-
Confidence interval
- ESI:
-
Electrospray ionization
- FDR:
-
False discovery rate
- GC:
-
Gastric cancer
- GGT:
-
γ-Glutamyl transferase
- GPT:
-
Glutamic pyruvate transaminase
- GOT:
-
Glutamic oxalacetic transaminase
- HDL:
-
High-density lipoprotein
- IS:
-
Internal standard
- KCPS:
-
Korean Cancer Prevention Study
- LDL:
-
Low-density lipoprotein
- m/z :
-
Mass-to-charge
- OPLS-DA:
-
Orthogonal projection to latent structures-discriminant analysis
- PRM:
-
Parallel reaction monitoring
- QC:
-
Quality control
- QE:
-
Q-exactive
- RSD:
-
Relative standard deviation
- RT:
-
Retention time
- TC:
-
Total cholesterol
- TG:
-
Triglyceride
- UHPLC:
-
Ultra-performance liquid chromatography
- VIP:
-
Variable importance in the projection
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Funding
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT of the Korea government (MSIT) [Grant Number: NRF-2020R1A2C2014374].
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YH designed the research, conducted the study, analyzed the data, performed the statistical analysis, wrote the original draft, and reviewed and edited the manuscript; HJY analyzed the data; SHJ designed the study, and provided essential materials; JHL designed the study, and reviewed the manuscript; SHJ and JHL had primary responsibility for the final content. All authors read and approved the final manuscript.
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Han, Y., Yoo, H.J., Jee, S.H. et al. High serum levels of l-carnitine and citric acid negatively correlated with alkaline phosphatase are detectable in Koreans before gastric cancer onset. Metabolomics 18, 62 (2022). https://doi.org/10.1007/s11306-022-01922-7
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DOI: https://doi.org/10.1007/s11306-022-01922-7