A Comprehensive Workflow of Mass Spectrometry-Based Untargeted Metabolomics in Cancer Metabolic Biomarker Discovery Using Human Plasma and Urine
Abstract
:1. Overview
1.1. Hyphenated Separation and Detection Techniques
1.2. Untargeted Metabolic Profiling
1.3. Data Mining Techniques
1.4. Annotation and Identification
1.5. Predictive MRM Screening of Secondary Metabolites.
1.6. Pathway Analysis
2. The Application in Early Diagnosis of Pancreatic Cancer
2.1. Introduction
2.2. Procedure
2.2.1. Material
2.2.2. Sample Preparation
2.2.3. Untargeted Metabolic Profiling
2.2.3.1. LC-MS
2.2.3.1.1. RP ESI-LC-MS
2.2.3.1.2. HILIC ESI-LC-MS
2.2.3.2. GC–MS
2.2.4. Data Mining
2.2.4.1. Free Open Source Software
2.2.4.2. Commercial Software
2.2.5. Annotation and Identification of Feature Components
2.2.5.1. Accurate Mass, Isotope Pattern, and MS/MS
2.2.5.2. MSn Ion Tree
2.2.6. Pathway Analysis
2.3. Results and Discussion
2.3.1. Experimental Design
2.3.2. Principal Component Analysis
2.3.3. Putative Biomarkers
Substance Name | PubChem CID | m/z-Ion polarity | Profiling Method | p-Value | Fold Change |
---|---|---|---|---|---|
Increased in PDAC | |||||
Arachidonic acid | 444899 | GC-TOF-MS | 0.040982 | 1.49 | |
Erythritol | 8998 | GC-TOF-MS | 0.008525 | 1.53 | |
Cholesterol | 5997 | GC-TOF-MS | 0.030047 | 1.85 | |
N-Methylalanine | 5288725 | GC-TOF-MS | 0.024311 | 2.81 | |
Lysine | 5962 | 147.1 pos | HILIC-LC/MS | 0.017356 | 1.03 |
Deoxycholylglycine | 9675 | 448.53 neg | HILIC/RP-LC/MS | 0.000052 | 1.31 |
Cholylglycine | 16219399 | 464.42 neg | HILIC/RP-LC/MS | 0.000001 | 2.61 |
LysoPC (16:0) | 86554 | 496.2 pos | HILIC-LC/MS | 0.000645 | 1.33 |
Tauroursodeoxycholic | 3034759 | 498.34 neg | RP-LC/MS | 0.004029 | 2.01 |
Taurocholic acid | 6675 | 514.1 neg | HILIC/RP-LC/MS | 0.000312 | 1.75 |
LysoPC(18:2) | 11988421 | 520.23 pos | RP-LC/MS | 0.013425 | 1.59 |
PE(26:0) | 9546763 | 606.23 neg | RP-LC/MS | 0.012072 | 1.81 |
PC (34:2) | 6021688 | 758.31 pos | HILIC-LC/MS | 0.008014 | 1.32 |
Unknown | 753.12 pos | HILIC-LC/MS | 0.000002 | 1.27 | |
Unknown | 265.07 pos | HILIC-LC/MS | 0.000005 | 1.17 | |
Unknown | 332.07 pos | HILIC-LC/MS | 0.000031 | 1.37 | |
Unknown | 633.19 pos | RP-LC/MS | 0.009372 | 1.8 | |
Unknown | 414.15 pos | RP-LC/MS | 0.006497 | 1.69 | |
Decreased in PDAC | |||||
Glutamine | 5961 | 145.22 neg | HILIC/RP-LC/MS | 0.000021 | 1.2 |
Hydrocinnamic acid | 107 | 149.12 neg | HILIC-LC/MS | 0.000252 | 1.38 |
Phenylalanine | 6140 | 166.12 pos | RP-LC/MS | 0.036583 | 1.15 |
Tryptamine | 1150 | 205.09 pos | RP-LC/MS | 0.016353 | 1.07 |
Inosine | 6021 | 267.21 neg | RP-LC/MS | 0.000014 | 1.4 |
Unknown | 187.12 neg | RP-LC/MS | 0.000246 | 1.11 |
2.3.4. Metabolite Network Analysis
2.3.5. Validation
2.3.6. Summary
3. The Application in Early Diagnosis of Kidney Cancer
3.1. Introduction
3.2. Procedure
3.2.1. Sample Preparation
3.2.2. Untargeted Screening Using Full Scan Mode (See Section 2)
3.2.3. Subclass Screening Using Neutral Loss Scan, Precursor Ion Scan, and Predictive MRM
3.3. Results and Discussion
3.3.1. Untargeted Profiling
3.3.2. Low Abundant Subclass Screening
3.3.3. Summary
4. Conclusions
Acknowledgements
Conflicts of Interest
References
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Zou, W.; She, J.; Tolstikov, V.V. A Comprehensive Workflow of Mass Spectrometry-Based Untargeted Metabolomics in Cancer Metabolic Biomarker Discovery Using Human Plasma and Urine. Metabolites 2013, 3, 787-819. https://doi.org/10.3390/metabo3030787
Zou W, She J, Tolstikov VV. A Comprehensive Workflow of Mass Spectrometry-Based Untargeted Metabolomics in Cancer Metabolic Biomarker Discovery Using Human Plasma and Urine. Metabolites. 2013; 3(3):787-819. https://doi.org/10.3390/metabo3030787
Chicago/Turabian StyleZou, Wei, Jianwen She, and Vladimir V. Tolstikov. 2013. "A Comprehensive Workflow of Mass Spectrometry-Based Untargeted Metabolomics in Cancer Metabolic Biomarker Discovery Using Human Plasma and Urine" Metabolites 3, no. 3: 787-819. https://doi.org/10.3390/metabo3030787