Table 2.
Metabolic Features in Pathways Associated with Aspirin Treatment: Fold changes with Aspirin and Associations with Adenoma Outcomes
| m/z | RT | Col | FC (95% CI)a 81 mg Aspirin | FC (95% CI)a 325 mg Aspirin | RR (95% CI)b Any Adenomac | RR (95% CI)b Advancedc | RR (95% CI)b High-Riskc | Putative Identityd | Adductd | MSI leveld |
|---|---|---|---|---|---|---|---|---|---|---|
| A. Metabolic features that decreased with aspirin treatment: | ||||||||||
| 88.012 | 19.3 | C18− | 0.74 (0.56–0.98) | 0.87 (0.74–1.03) | 0.94 (0.91–1.02) | 0.95 (0.83–1.12) | 0.89 (0.83–1.02) | Pyruvate | M(C13)−H | 1 |
| 103.0591 | 18.7 | C18− | 0.74 (0.55–1.00) | 1.07 (0.91–1.25) | 0.94 (0.91–1.01) | 1.17 (0.93–1.35) | 0.87 (0.83–0.99) | 2-aminobutyrate | M(C13)−H | 1 |
| 156.0288 | 26.4 | C18− | 0.49 (0.26–0.90) | 0.68 (0.39–1.17) | 1.02 (0.98–1.05) | 0.97 (0.91–1.05) | 0.96 (0.92–1.03) | N-Acetyl-L-aspartate | M−H2O−H | 1 |
| 171.0069 | 18.4 | C18− | 0.57 (0.34–0.96) | 0.78 (0.51–1.21) | 1.02 (0.97–1.06) | 1.10 (1.00–1.14) | 1.12 (1.02–1.15) | Glycerol 3-phosphate | M−H | 1 |
| 173.0569 | 24.2 | C18− | 0.56 (0.33–0.97) | 0.79 (0.50–1.25) | 1.00 (0.97–1.03) | 0.93 (0.89–1.02) | 0.92 (0.90–1.00) | 5,6-Dihydrouracil | M+CH3COO | 2 |
| 191.0679 | 19.9 | C18− | 0.54 (0.29–0.99) | 0.86 (0.51–1.44) | 1.02 (0.98–1.05) | 1.04 (0.94–1.12) | 0.99 (0.93–1.06) | L-Asparagine | M+CH3COO | 1 |
| 231.1358 | 20.2 | C18− | 0.38 (0.18–0.83) | 1.24 (0.65–2.36) | 1.01 (0.98–1.03) | 1.03 (0.96–1.08) | 1.02 (0.97–1.07) | Spermic acid 2 | M−H | 2 |
| 319.2253 | 35 | HILIC+ | 0.77 (0.43–1.38) | 0.48 (0.24–0.96) | 1.00 (0.98–1.03) | 1.00 (0.93–1.08) | 0.97 (0.93–1.03) | Leukotriene A4 | M+H | 2 |
| 335.2205 | 30.2 | HILIC+ | 0.81 (0.46–1.43) | 0.43 (0.21–0.84) | 0.98 (0.96–1.01) | 1.04 (0.96–1.10) | 0.97 (0.93–1.03) | Prostaglandin C2e | M+H | 2 |
| 336.2241 | 25.6 | HILIC+ | 0.76 (0.42–1.38) | 0.42 (0.21–0.83) | 0.99 (0.97–1.02) | 1.06 (0.96–1.12) | 1.01 (0.95–1.07) | 12,13-DHOME | M+Na | 2 |
| 351.2180 | 23 | C18− | 0.66 (0.27–1.63) | 0.20 (0.08–0.54) | 0.98 (0.97–1.01) | 0.98 (0.94–1.03) | 0.96 (0.94–1.01) | Alpha-Hydroxy-9,15-dioxoprostanoatee,f | M−H | 2 |
| 370.2323 | 21.2 | C18− | 0.34 (0.16–0.70) | 0.31 (0.15–0.64) | 1.00 (0.98–1.03) | 1.01 (0.94–1.07) | 1.00 (0.95–1.06) | Thromboxane B2f | M(C13)−H | 2 |
| B. Metabolic features that increased with aspirin treatment: | ||||||||||
| 261.2224 | 244.8 | C18− | 1.35 (1.02–1.78) | 0.92 (0.61–1.38) | 0.95 (0.93–1.00) | 0.92 (0.85–1.04) | 0.94 (0.87–1.06) | Linoleate | M−H2O−H | 1 |
| 400.3402 | 24.8 | HILIC+ | 1.30 (0.92–1.83) | 1.36 (1.01–1.84) | 1.22 (1.06–1.24) | 1.41 (0.92–1.75) | 1.36 (0.95–1.60) | L-Palmitoylcarnitine | M+H | 1 |
| 426.3568 | 24.8 | HILIC+ | 1.39 (0.95–2.04) | 1.50 (1.08–2.10) | 1.18 (1.04–1.20) | 1.23 (0.90–1.48) | 1.25 (0.95–1.44) | Octadecenoyl carnitinee | M+H | 2 |
| 428.3716 | 25 | HILIC+ | 1.24 (0.91–1.70) | 1.38 (1.08–1.76) | 1.22 (1.04–1.26) | 1.43 (0.94–1.75) | 1.44 (0.99–1.67) | Stearoylcarnitine | M+H | 1 |
| 448.3429 | 23.9 | HILIC+ | 1.83 (1.06–3.15) | 1.03 (0.53–2.00) | 1.05 (0.99–1.08) | 1.00 (0.92–1.09) | 1.04 (0.94–1.12) | C20:4 carnitinee | M+H | 2 |
| 450.3572 | 24.5 | HILIC+ | 2.49 (1.18–5.26) | 1.58 (0.71–3.51) | 1.02 (0.99–1.04) | 1.03 (0.95–1.09) | 1.03 (0.96–1.09) | Dihomo-gamma-linolenyl carnitinee | M+H | 2 |
| 456.4043 | 25.3 | HILIC+ | 2.68 (1.34–5.35) | 1.65 (0.79–3.46) | 1.03 (0.99–1.05) | 0.99 (0.93–1.06) | 1.01 (0.95–1.06) | Arachidyl carnitine | M+H | 1 |
| 476.3729 | 24.5 | HILIC+ | 2.30 (1.04–5.07) | 2.64 (1.21–5.78) | 1.01 (0.99–1.03) | 1.08 (0.99–1.13) | 1.06 (0.98–1.10) | Adrenyl carnitine | M+H | 2 |
NOTE: Only metabolic features from pathways associated with aspirin treatment in Figure 3 are included.
Abbreviations: RT, retention time in seconds; Col, chromatography column (C18 or HILIC) and ionization mode (− or +); FC; fold change; RR, risk ratio; CI, confidence interval; MSI, Metabolomics Standards Initiative; 12,13-DHOME, 12,13-hydroxyoctadec-9(Z)-enoate.
Linear regression was used to estimate the fold change in year 3 ion intensities in the aspirin treatment group compared to the placebo treatment group, adjusting for age, sex, race, and folate treatment. Bolding indicates statistically significant (P<0.05).
Poisson regression was used to assess the association of risk of adenoma outcomes with a two-fold change in ion intensity, adjusting for age, sex, and race. Bolding indicates statistically significant (P<0.05).
Any adenoma refers to ≥1 adenoma of any type; advanced refers to adenomas with cancer, high-grade dysplasia, >25% villous component, or diameter ≥1 cm; high-risk refers to ≥1 advanced adenoma or ≥3 adenomas of any type.
For putative identities shown, the adduct form and MSI identification confidence level are indicated in the columns to the right.
For these metabolic features, an additional adduct form was detected but is not shown to reduce redundancy in the table.
In pathway analysis, two metabolic features in the Prostaglandin Formation from Arachidonate pathway were associated with any aspirin treatment (combined analysis of 81 and 325 mg), but not either dose alone.