Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants and Sample Collection
2.2. NMR Analysis
2.3. Mass Spectrometry Analysis
2.4. Standards
2.5. Sample Processing
2.6. LC-MS Analysis
2.7. Statistical Analysis
3. Results
3.1. Participant Characteristics
3.2. Key Metabolite Identification
4. LC-MS Measurements
4.1. Development and Validation of the MS Based Test
4.2. Comparison of the MS-Based Metabolomics Test with NMR-Based Test
4.3. Comparison of the MS-Based Urine Metabolomics Test with Commercially Available Fecal-Based Tests
5. Discussion
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Label | Colonoscopy Results | Age | Sex | Smoker |
---|---|---|---|---|
Normal | Normal (n = 446) | μ = 56.1 | F = 308 | Yes = 50 |
n = 530 | Hyperplastic (n =84) | σ = 8.2 | M = 222 | Ex-Smoker = 12 |
No = 449 | ||||
Unknown = 19 | ||||
Polyp | Adenoma (n = 154) | μ = 59.9 | F = 60 | Yes = 26 |
n = 155 | CRC (n = 1) | σ = 7.4 | M = 95 | Ex-Smoker = 4 |
No = 119 | ||||
Unknown = 6 |
P-Value | Metabolite |
---|---|
0.0059 | Succinic acid |
0.0100 | Ascorbic acid |
0.0280 | Carnitine |
0.0595 | Creatine |
0.0739 | Citric acid |
0.0861 | Methylamine |
0.0945 | Pantothenic acid |
0.1198 | Fumaric acid |
0.1346 | 1-Methylnicotinamide |
0.1703 | Trigonelline |
Training Set | Testing Set | |||||||
---|---|---|---|---|---|---|---|---|
Threshold Criteria | Sensitivity | Specificity | PPV | NPV | Sensitivity | Specificity | PPV | NPV |
Urine tests | ||||||||
Sens = 90% (95% CI *) | 90.3% (84.6–96.0%) | 20.9% (16.7–25.1%) | 24.9% | 88.0% | 92.2% (84.8–99.5%) | 19.2% (13.3–25.1%) | 25.3% | 89.2% |
Sens = 80% (95% CI) | 79.6% (71.8–87.4%) | 42.1% (36.9–47.2%) | 28.6% | 87.7% | 82.4% (71.9–92.8%) | 36.0% (28.9–43.2%) | 27.6% | 87.3% |
Sens = 70% (95% CI) | 69.9% (61.0–78.8%) | 59.0% (53.9–64.2%) | 33.2% | 87.1% | 66.7% (53.7–79.6%) | 55.2% (47.8–62.7%) | 30.6% | 84.8% |
Spec = 70% (95% CI) | 59.2% (49.7–68.7%) | 70.1% (65.3–74.8%) | 36.5% | 85.5% | 56.9% (43.3–70.5%) | 70.9% (64.1–77.4%) | 35.4% | 84.7% |
Spec = 80% (95% CI) | 46.6% (37.2–56.2%) | 80.0% (75.8–84.1%) | 40.3% | 83.7% | 49.0% (35.3–62.7%) | 80.8% (74.9–86.7%) | 43.1% | 84.2% |
Spec = 90% (95% CI) | 31.1% (22.1–40.0%) | 88.1% (84.8–91.5%) | 43.2% | 81.4% | 43.1% (29.5–56.7%) | 91.3% (87.1–95.5%) | 59.5% | 84.4% |
Fecal Tests | ||||||||
Guaiac HemII | 2.0% | 98.8% | 33.3% | 77.5% | 3.8% | 99.4% | 66.7% | 77.1% |
Immune ICT | 10.9% | 97.1% | 52.4% | 78.7% | 17.6% | 97.0% | 64.3% | 79.6% |
Immune MagSt | 15.8% | 95.4% | 50.0% | 79.5% | 21.2% | 91.7% | 44.0% | 79.1% |
Feature | PubChem CID | HMDB | Correlation |
---|---|---|---|
Smoker | N/A | N/A | 0.09 |
Age | N/A | N/A | 0.13 |
Sex | N/A | N/A | 0.17 |
Succinic Acid | 1110 | HMDB00254 | −0.16 |
Ascorbic Acid | 54670067 | HMDB00044 | −0.15 |
Carnitine | 2724480 | HMDB00062 | −0.13 |
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Deng, L.; Chang, D.; Foshaug, R.R.; Eisner, R.; Tso, V.K.; Wishart, D.S.; Fedorak, R.N. Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps. Metabolites 2017, 7, 32. https://doi.org/10.3390/metabo7030032
Deng L, Chang D, Foshaug RR, Eisner R, Tso VK, Wishart DS, Fedorak RN. Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps. Metabolites. 2017; 7(3):32. https://doi.org/10.3390/metabo7030032
Chicago/Turabian StyleDeng, Lu, David Chang, Rae R. Foshaug, Roman Eisner, Victor K. Tso, David S. Wishart, and Richard N. Fedorak. 2017. "Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps" Metabolites 7, no. 3: 32. https://doi.org/10.3390/metabo7030032
APA StyleDeng, L., Chang, D., Foshaug, R. R., Eisner, R., Tso, V. K., Wishart, D. S., & Fedorak, R. N. (2017). Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps. Metabolites, 7(3), 32. https://doi.org/10.3390/metabo7030032