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LC-MS/MS and SWATH based serum metabolomics enables biomarker discovery in pancreatic cancer
- Source :
- Clinica chimica acta; international journal of clinical chemistry. 506
- Publication Year :
- 2019
-
Abstract
- Background Pancreatic cancer (PC) is the fourth leading cause of cancer death because of its subtle clinical symptoms in the early stage. To discover particular serum metabolites as potential biomarkers to differentiate pancreatic carcinoma from benign disease (BD) is on urgent demand. Method To comprehensively analyze serum metabolites obtained from 14 patients with PC, 10 patients with BD and 10 healthy individuals (normal control, NC), we separated the metabolites using both reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC). The data were acquired on a high-resolution quadrupole time-of-flight mass spectrometer operated in negative (ESI–) and positive (ESI+) ionization modes, respectively. Differential metabolites were selected by univariate (Student’s t test) and multivariate (orthogonal partial least squares-discriminant analysis (OPLS-DA)) statistics. Sequential window acquisition of all theoretical spectra (SWATH) analysis was further utilized to validate the metabolites found in discovery stage. The receiver operator characteristics (ROC) curve analysis was performed to evaluate predictive clinical usefulness of 8 metabolites. Results A total of 8 metabolites including taurocholic acid, glycochenodexycholic acid, glycocholic acid, L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine were identified and relatively quantified as differential metabolites for discriminating PC, BD and NC. The 8 metabolites and their combination discriminated PC from BD and NC with well-performed area under the curve (AUC) values, sensitivity and specificity. Conclusion Bile acids (especially taurocholic acid) performed to be potential biomarkers in PC diagnosis. Other amino acids (such as L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine) in serum samples from PC patients might provide a sensitive, blood-borne diagnostic signature for the presence of PC or its precursor lesions.
- Subjects :
- 0301 basic medicine
Quality Control
Clinical Biochemistry
Glycocholic acid
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Metabolomics
Tandem Mass Spectrometry
Pancreatic cancer
medicine
Biomarkers, Tumor
Humans
Biomarker discovery
Chromatography
Chemistry
Hydrophilic interaction chromatography
Biochemistry (medical)
Area under the curve
General Medicine
medicine.disease
Taurocholic acid
Pancreatic Neoplasms
030104 developmental biology
030220 oncology & carcinogenesis
Multivariate Analysis
Biomarker (medicine)
Chromatography, Liquid
Subjects
Details
- ISSN :
- 18733492
- Volume :
- 506
- Database :
- OpenAIRE
- Journal :
- Clinica chimica acta; international journal of clinical chemistry
- Accession number :
- edsair.doi.dedup.....03d1191f52df16a233ffc1dfda1fb3c3