NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethical Statement
2.2. Study Participants
2.3. Pre-Analytical Plasma Sample Preparation
2.4. 1H-NMR Analysis and Processing
2.5. Data Analysis by Multivariate and Univariate Statistics
2.5.1. Multivariate Discriminant Analysis
2.5.2. Identification of Differentiating Variables
2.5.3. Selection of Differentiating Variables Corresponding to a Single Metabolite
2.5.4. Univariate Statistics
3. Results
3.1. Patient Population and Study Design
3.2. Baseline (B) versus Effect (E): Tumor Resection Causes a Shift in The Plasma Metabolite Profile of NSCLC Patients
3.3. Control (C) versus Effect (E): The Preoperative Metabolite Profile Can Be Determined at the Moment of NSCLC Diagnosis
3.4. Baseline (B) versus Control (C): The NSCLC Metabolite Profile Is Patient-Specific before Surgery
3.5. Lactate, Cysteine, Asparagine and Acetate Are Identified as Key Contributors to the Metabolic Shift after NSCLC Surgery
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Training Cohort | Validation Cohort | ||
---|---|---|---|
Number of patients, n | 50 | 24 | |
Sex, n (%) | Male | 27 (54) | 15 (63) |
Female | 23 (46) | 9 (37) | |
Age, years (range) | 68 ± 8 (45–83) | 68 ± 9 (47–82) | |
BMI, kg/m2 (range) | 26.9 ± 5.5 (16.6–50.4) | 25.7 ± 3.8 (17.4–32.9) | |
Diabetes, n (%) | 11 (22) | 4 (17) | |
COPD, n (%) | 11 (22) | 5 (21) | |
Smoking status, n (%) | Active smoker | 24 (48) | 12 (50) |
Ex-smoker (stopped > 6 months) | 25 (50) | 10 (42) | |
Non-smoker | 1 (2) | 2 (8) | |
Pathological tumor stage, n (%) | 0 | 1 (2) | 0 (0) |
IA1 | 3 (6) | 1 (4) | |
IA2 | 21 (42) | 5 (21) | |
IA3 | 7 (14) | 5 (21) | |
IB | 5 (10) | 7 (29) | |
IIA | 1 (2) | 1 (4) | |
IIB | 6 (12) | 0 (0) | |
IIIA | 6 (12) | 5 (21) | |
Number of tumors, n | 53 | 25 | |
NSCLC tumor histology, n (%) | Adenocarcinoma | 34 (64) | 16 (64) |
Squamous carcinoma | 13 (25) | 8 (32) | |
Adenosquamous carcinoma | 1 (2) | 0 (0) | |
Neuroendocrine carcinoma | 5 (9) | 1 (4) | |
LVI, n (%) | Negative | 44 (83) | 17 (68) |
Positive | 9 (17) | 8 (32) | |
VPI, n (%) | Negative | 45 (85) | 18 (72) |
Positive | 8 (15) | 7 (28) | |
Resection margin, n (%) | R0 | 50 (94) | 25 (100) |
R1 | 3 (6) | 0 (0) |
B/E | C/E | B/C | ||||
---|---|---|---|---|---|---|
OPLS-DA | OPLS-EP | OPLS-DA | OPLS-EP | OPLS-DA | ||
TRAINING | ||||||
Number of patients, n (number of samples, s) | 50 (100) | 50 (100) | 50 (100) | 50 (100) | 50 (100) | |
R2X (cum) | 0.55 | 0.59 | 0.53 | 0.57 | 0.31 | |
R2Y (cum) | 0.67 | 0.89 | 0.61 | 0.83 | 0.15 | |
Q2 (cum) | 0.42 | 0.76 | 0.36 | 0.60 | 0.08 | |
Specificity (%) | 96 (86–100) | / | 90 (78–97) | / | 62 (47–75) | |
Sensitivity (%) | 92 (81–98) | / | 88 (76–95) | / | 74 (60–85) | |
Accuracy (%) | 94 (87–98) | 86 | 89 (81–94) | 84 | 68 (58–77) | |
Fisher’s probability/ CV-ANOVA p-value | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | |
AUC | 0.99 (0.98–1) | / | 0.97 (0.94–1) | / | 0.72 (0.62–0.82) | |
VALIDATION | ||||||
Number of patients, n (number of samples, s) | 24 (48) | 24 (48) | 23 (46) | 23 (46) | 23 (46) | |
Specificity (%) | 92 (73–99) | / | 91 (72–99) | / | 43 (23–66) | |
Sensitivity (%) | 88 (68–97) | / | 96 (78–100) | / | 74 (52–90) | |
Accuracy (%) | 90 (77–97) | 92 | 93 (82–99) | 87 | 59 (42–73) | |
Fisher’s probability p-value | <0.001 | / | <0.001 | / | 0.18 | |
AUC | 0.97 (0.93–1) | / | 0.97 (0.93–1) | / | 0.69 (0.53–0.84) |
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Derveaux, E.; Geubbelmans, M.; Criel, M.; Demedts, I.; Himpe, U.; Tournoy, K.; Vercauter, P.; Johansson, E.; Valkenborg, D.; Vanhove, K.; et al. NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer. Cancers 2023, 15, 2127. https://doi.org/10.3390/cancers15072127
Derveaux E, Geubbelmans M, Criel M, Demedts I, Himpe U, Tournoy K, Vercauter P, Johansson E, Valkenborg D, Vanhove K, et al. NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer. Cancers. 2023; 15(7):2127. https://doi.org/10.3390/cancers15072127
Chicago/Turabian StyleDerveaux, Elien, Melvin Geubbelmans, Maarten Criel, Ingel Demedts, Ulrike Himpe, Kurt Tournoy, Piet Vercauter, Erik Johansson, Dirk Valkenborg, Karolien Vanhove, and et al. 2023. "NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer" Cancers 15, no. 7: 2127. https://doi.org/10.3390/cancers15072127