Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Patient Selection and Classification
4.2. Biospecimen Collection
4.3. Laboratory Analyses and Quality Control Measurements
4.4. Sample Preparation and Quality Control: GC–MS
4.5. Sample Preparation and Quality Control: 1H-NMR
4.6. Data Pre-Processing
4.7. Normalization of Metabolite Concentrations
4.8. Area-Based Computed Tomography (CT) Quantification of Abdominal Adipose Tissue and Muscle Tissue Area
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Category | Weight Loss | BMI |
---|---|---|
Non-Cachectic | weight loss ≤ 2% weight gain | - |
Pre-Cachectic | weight loss * ≤ 5% | BMI ≤ 20 kg/m2 |
Cachectic | weight loss * > 5% | |
Cachectic | weight loss * > 2% | BMI < 20 kg/m2 |
Cachectic (n = 16) | Pre-Cachectic (n = 13) | Non-Cachectic (n = 23) | p-Value | |
---|---|---|---|---|
Age at surgery + | 58.38 (±10.33) | 55.84 (±11.67) | 62.74 (±12.22) | 0.21 + |
BMI 1 (kg/m2) | ||||
at Baseline 2,+ | 25.60 (±2.71) | 29.39 (±3.35) | 26.48 (±4.26) | 0.02 + |
6 Months afterwards 3,+ | 23.37 (±3.08) | 28.11 (±3.42) | 26.54 (±4.41) | 0.004 + |
Weight Change (kg) + | −7.12 (±3.63) | −2.54 (±1.27) | 2.78 (±2.68) | <0.001 + |
Weight Change (%) | −0.09 (±0.05) | −0.02 (±0.02) | 0.03 (±0.03) | <0.001 + |
Sex | 0.33 ++ | |||
Male | 11 (69%) | 11 (85%) | 14 (61%) | |
Female | 5 (31%) | 2 (15%) | 9 (39%) | |
Stage | 0.11 ++ | |||
I | 5 (31%) | 2 (15%) | 7 (30%) | |
II | 1 (6%) | 5 (38%) | 9 (40%) | |
III | 6 (38%) | 4 (31%) | 7 (30%) | |
IV | 4 (25%) | 2 (15%) | 0 | |
Site | 0.58 ++ | |||
Colon | 6 (38%) | 5 (38%) | 12 (52%) | |
Rectal | 10 (62%) | 8 (62%) | 11(48%) | |
Adjuvant Therapy | 0.14 ++ | |||
Yes | 10 (62%) | 8 (62%) | 7 (30%) | |
No | 6 (38%) | 5 (38%) | 16 (70%) | |
Neo-Adjuvant Therapy | 0.43 ++ | |||
Yes | 6 (38%) | 4 (31%) | 6 (26%) | |
No | 10 (62%) | 9 (70%) | 17 (74%) |
Cachectic (n = 16) | Pre-Cachectic | Non-Cachectic | p-Value for Group Comparisons | ||||
---|---|---|---|---|---|---|---|
(n = 13) | (n = 23) | Three Group Comparison | Cachectic vs Non-Cachectic | Cachectic vs Pre-Cachectic | Pre-Cachectic vs Non-Cachectic | ||
Visceral Fat Area | |||||||
L3/L4 | 152.93 (±92.56) | 231.20 (±68.97) | 184.26 (±68.59) | 0.08 | 0.34 | 0.04 | 0.11 |
L4/L5 | 134.90 (±74.86) | 204.51 (±57.86) | 154.96 (±51.81) | 0.04 | 0.44 | 0.03 | 0.04 |
Subcutaneous Fat Area | |||||||
L3/L4 | 204.58 (±101.90) | 301.70 (±125.96) | 255.47 (±130.21) | 0.20 | 0.30 | 0.06 | 0.39 |
L4/L5 | 230.00 (±97.10) | 320.38 (±111.91) | 286.10 (±125.43) | 0.19 | 0.23 | 0.06 | 0.50 |
Dorsal muscle Area | |||||||
L3/L4 | 37.77 (±14.86) | 30.31 (16.34) | 35.43 (17.25) | 0.57 | 0.72 | 0.29 | 0.47 |
L4/L5 | 29.44 (±10.26) | 21.84 (14.66) | 27.93 (11.34) | 0.32 | 0.73 | 0.18 | 0.26 |
Psoas muscle Area | |||||||
L3/L4 | 19.30 (±8.57) | 18.55 (±6.19) | 19.34 (±6.86) | 0.96 | 0.98 | 0.82 | 0.77 |
L4/L5 | 28.81 (±24.44) | 19.29 (±6.58) | 22.30 (±7.93) | 0.34 | 0.36 | 0.25 | 0.34 |
Abdominal muscle Area | |||||||
L3/L4 | 42.88 (±17.46) | 26.02 (±14.07) | 34.25 (±15.12) | 0.06 | 0.20 | 0.03 | 0.19 |
L4/L5 | 36.07 (±14.49) | 24.92 (±14.58) | 30.01 (±15.61) | 0.24 | 0.33 | 0.09 | 0.43 |
Platform | Metabolite (mean ± std) | Cachectic | Non-Cachectic | Fold Change | pValue1 | pFDR2 | Identification |
---|---|---|---|---|---|---|---|
GC–MS 3 | 2.3-Butanediol | 0.2 ± 0.76 | 1.0 ± 0.73 | 0.45 | 0.01 | 0.93 | Level 2 |
2.3-Dihydroxybutyrate | 0.1 ± 0.59 | −0.5 ± 0.56 | 1.82 | 0.02 | 0.93 | Level 2 | |
Sugar 15.798 min | 0.3 ± 1.02 | 1.1 ± 0.89 | 0.45 | 0.04 | 0.93 | Level 3 | |
4-Hydroxyphenylacetate | −0.2 ± 0.67 | 0.5 ± 0.98 | 0.50 | 0.04 | 0.93 | Level 2 | |
Unknown Glucuronide 28.543 min | 0.3 ± 0.66 | 0.9 ± 0.98 | 0.55 | 0.04 | 0.93 | Level 3 | |
1H-NMR 4,5 | 3-Methylxanthine | 3.3 ± 1.81 | 5.8 ± 2.87 | 0.76 | 0.02 | 0.97 | NMR library |
Acetone | 7.1 ± 7.37 | 1.7 ± 1.01 | 3.17 | 0.02 | 0.97 | NMR library | |
Arginine | 25.8 ± 6.66 | 19.4 ± 8.03 | 0.33 | 0.04 | 0.97 | NMR library |
Platform | Metabolite (Mean ± Std) | Cachectic | Pre-Cachectic | Fold Change | pValue1 | pFDR2 | Identification |
---|---|---|---|---|---|---|---|
GC-MS 3 | Hydroquinone | 0.6 ± 0.49 | −0.5 ± 1.20 | 3.00 | 0.006 | 0.59 | Level 1 |
Unknown 13.271 min | 0.0 ± 0.86 | 0.8 ± 0.80 | 0.45 | 0.009 | 0.59 | Level 4 | |
Aminomalonate | 0.4 ± 0.59 | −0.3 ± 0.77 | 2.01 | 0.01 | 0.59 | Level 2 | |
Sugar Acid 15.429 min | 0.5 ± 0.74 | −0.1 ± 0.55 | 1.82 | 0.01 | 0.60 | Level 3 | |
4-Hydroxy-3-Methoxy-Mandelate | 0.6 ± 1.15 | −0.3 ± 0.83 | 2.46 | 0.03 | 0.79 | Level 2 | |
Unknown Glucuronide 29.801 min | 0.7 ± 0.79 | 0.0 ± 1.06 | 2.01 | 0.03 | 0.79 | Level 3 | |
Sugar Acid 15.750 min | 0.6 ± 0.79 | −0.1 ± 1.16 | 2.01 | 0.04 | 0.79 | Level 3 | |
Unknown Sugar 14.575 min | 0.4 ± 0.94 | −0.4 ± 1.23 | 2.23 | 0.04 | 0.79 | Level 3 | |
Unknown Dissacharide 29.943 min | 0.5 ± 0.76 | −0.2 ± 1.12 | 2.01 | 0.04 | 0.79 | Level 3 | |
1H-NMR 4,5 | Isobutyrate | 0.8 ± 0.78 | 1.7 ± 1.21 | 1.13 | 0.02 | 0.97 | NMR library |
0.79 | |||||||
Glycine | 150.1 ± 118.51 | 72.5 ± 42.98 | 1.07E+33 | 0.04 | 0.97 | NMR library |
Platform | Metabolite (Mean ± Std) | Pre-Cachectic | Non-Cachectic | Fold Change | pValue1 | pFDR2 | Identification |
---|---|---|---|---|---|---|---|
GC-MS 3 | Sugar Acid 15.429 min | −0.1 ± 0.55 | 0.8 ± 0.86 | 0.41 | 0.007 | 0.59 | Level 3 |
2-O-Glycerol-α-d-galactopyranoside | −0.4 ± 1.09 | 0.6 ± 0.49 | 0.37 | 0.01 | 0.59 | Level 2 | |
Sugar 15.798 min | 0.0 ± 1.06 | 1.1 ± 0.89 | 0.33 | 0.01 | 0.59 | Level 3 | |
Tartrate | 0.0 ± 0.85 | 1.0 ± 1.07 | 0.37 | 0.01 | 0.59 | Level 1 | |
Hydroquinone | −0.5 ± 1.20 | 0.7 ± 1.14 | 0.30 | 0.02 | 0.59 | Level 1 | |
Sugar Acid 15.750 min | −0.1 ± 1.16 | 0.8 ± 0.61 | 0.41 | 0.03 | 0.59 | Level 3 | |
Unknown 28.636 min | 0.1 ± 1.14 | 1.1 ± 0.94 | 0.37 | 0.03 | 0.59 | Level 4 | |
Unknown Glucuronide 27.116 min | 0.0 ± 0.83 | 0.7 ± 0.67 | 0.50 | 0.03 | 0.59 | Level 3 | |
Unknown Glucuronide 28.543 min | 0.1 ± 0.89 | 0.9 ± 0.98 | 0.45 | 0.04 | 0.59 | Level 3 | |
Sugar 14.052 min | −0.4 ± 1.34 | 0.7 ± 1.02 | 0.33 | 0.04 | 0.59 | Level 3 | |
p-cresol-glucuronide | −0.3 ± 1.27 | 0.6 ± 0.68 | 0.41 | 0.04 | 0.59 | Level 1 | |
Unknown Glucuronide 27.688 min | 0.1 ± 0.86 | 0.9 ± 0.75 | 0.45 | 0.04 | 0.59 | Level 3 | |
Unknown Glucuronide 29.801 min | 0.0 ± 1.06 | 0.8 ± 0.90 | 0.45 | 0.049 | 0.59 | Level 3 | |
1H-NMR 4,5 | Uracil | 6.5 ± 2.10 | 3.9 ± 2.15 | 0.67 | 0.008 | 0.91 | NMR library |
Cholate | 0.8 ± 0.12 | 1.6 ± 0.27 | 1.00 | 0.03 | 0.91 | NMR library | |
Methionine | 4.4 ± 2.54 | 2.2 ± 1.37 | 1.00 | 0.03 | 0.91 | NMR library | |
Acetone | 3.2 ± 1.83 | 1.7 ± 1.01 | 0.88 | 0.03 | 0.91 | NMR library | |
3-Phenylpropionate | 9.1 ± 3.97 | 14.4 ± 6.05 | 0.58 | 0.03 | 0.91 | NMR library | |
Arginine | 28.7 ± 11.98 | 19.4 ± 8.03 | 0.48 | 0.045 | 0.91 | NMR library |
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Ose, J.; Gigic, B.; Lin, T.; Liesenfeld, D.B.; Böhm, J.; Nattenmüller, J.; Scherer, D.; Zielske, L.; Schrotz-King, P.; Habermann, N.; et al. Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study. Metabolites 2019, 9, 178. https://doi.org/10.3390/metabo9090178
Ose J, Gigic B, Lin T, Liesenfeld DB, Böhm J, Nattenmüller J, Scherer D, Zielske L, Schrotz-King P, Habermann N, et al. Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study. Metabolites. 2019; 9(9):178. https://doi.org/10.3390/metabo9090178
Chicago/Turabian StyleOse, Jennifer, Biljana Gigic, Tengda Lin, David B. Liesenfeld, Jürgen Böhm, Johanna Nattenmüller, Dominique Scherer, Lin Zielske, Petra Schrotz-King, Nina Habermann, and et al. 2019. "Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study" Metabolites 9, no. 9: 178. https://doi.org/10.3390/metabo9090178