Untargeted Metabolomic Characterization of Ovarian Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Sample Enrollment
2.2. Metabolic Profile of Urine and Plasma in Ovarian Carcinoma
2.3. Differential Putative Metabolites and Category
2.4. Diagnostic Model
2.5. Diagnosis Performance of Biomarkers Combined to Clinical Indicator
2.6. Early Diagnosis of Ovarian Carcinoma
3. Discussion
4. Materials and Methods
4.1. Participants and Study Design
4.2. HPLC-MS Analysis
4.2.1. Sample Preparation
4.2.2. Liquid Chromatography-Mass Spectrometry
4.3. Data Statistics and Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
OC | Ovarian Cancer |
BOT | Benign Ovarian Tumor |
UHPLC-QTOF-MS | Ultra-High-Performance Liquid Chromatography Quadrupole Time-of-flight Mass Spectrometry |
CA125 | Cancer Antigen 125 |
HE4 | Human Epididymis Protein 4 |
QC | Quality Control |
PCA | Principal Component Analysis |
OPLS-DA | Orthogonal Partial Least-Squared Discriminant Analysis |
PLS-DA | Partial Least-Squared Discriminant Analysis |
VIP | Variable important in the Projection |
FDR | False Discovery Rate |
SVM | Support Vector Machine |
ROC | Receiver Operating Characteristic Curve |
AUC | Area Under Curve |
PS | Phosphatidylserine |
PU | plasma polar sample |
PL | plasma nonpolar sample (PL) |
UU | urine polar sample |
UL | urine nonpolar sample |
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Discovery Set | Validation Set | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Plasma/Urine | Plasma | Urine | ||||||||||
Level | Normal | Benignant | Borderline | Malignant | Normal | Benignant | Borderline | Malignant | Normal | Benignant | Borderline | Malignant |
n | 40 | 36 | 13 | 74 | 36 | 14 | 1 | 21 | 40 | 45 | 7 | 76 |
Age (mean (sd)) | 39.67 (8.50) | 43.33 (14.55) | 46.54 (17.59) | 56.19 (9.77) | 40.83 (10.17) | 44.36 (17.08) | 34 | 54.76 (11.84) | 45.85 (9.72) | 43.51 (14.81) | 38.86 (13.87) | 53.75 (10.00) |
CA125 (mean (sd)) | 8.35 (5.81) | 83.45 (234.82) | 183.88 (326.63) | 1254.34 (1597.27) | 6.31 (3.78) | 60.96 (146.43) | 250.2 | 938.10 (1243.80) | 7.65 (6.12) | 94.57 (321.85) | 193.12 (140.65) | 1078.35 (1195.30) |
HE4 (mean (sd)) | - | 53.71 (13.77) | 84.34 (66.89) | 440.62 (447.08) | - | 52.28 (10.99) | 74.06 | 389.75 (472.48) | - | 49.93 (23.99) | 93.45 (40.62) | 519.58 (405.72) |
FIGO (%) | - | - | - | - | - | - | - | - | - | - | - | |
I | - | - | 8 (61.5) | 8 (10.8) | - | - | - | 2 (9.5) | - | - | 6 (85.7) | 13 (17.1) |
II | - | - | 1 (7.7) | 9 (12.2) | - | - | 1 (100.0) | 3 (14.3) | - | - | - | 7 (9.2) |
III | - | - | 2 (15.4) | 50 (67.6) | - | - | - | 15 (71.4) | - | - | 1 (14.3) | 51 (67.1) |
IV | - | - | - | 7 (9.5) | - | - | - | - | - | - | - | 5 (6.6) |
NA | 40 (100.0) | 36 (100.0) | 2 (15.4) | - | 36 (100.0) | 14 (100.0) | - | 1 (4.8) | 40 (100.0) | 45 (100.0) | - | - |
Pathology (%) | ||||||||||||
HGSOC | - | - | - | 57 (77.0) | - | - | - | 14 (70.0) | - | - | - | 56 (73.7) |
OCS | - | - | - | 1 (1.4) | - | - | - | 3 (15.0) | - | - | - | 3 (3.9) |
OCCC | - | - | - | 3 (4.1) | - | - | - | 2 (10.0) | - | - | - | 4 (5.3) |
OEC | - | - | - | - | - | - | - | - | - | - | - | 4 (5.3) |
Others | - | - | - | 13 (17.5) | - | - | - | 2 (10.0) | - | - | - | 9 (11.8) |
Compound_Name | RT (min) | m/z | Delta (ppm) | p-Value | FDR | log2FC | VIP | Super Class | Class | Direct Parent |
---|---|---|---|---|---|---|---|---|---|---|
Normal vs. Ovarian tumor (Urine) | ||||||||||
1-(2,4,12-Octadecatrienoyl) piperidine | 3.2758 | 363.329 | 5.47 | 7.16 × 10−23 | 5.17 × 10−22 | −2.7274 | 1.2971 | Organoheterocyclic compounds | Piperidines | N-acylpiperidines |
PS(46:1) | 5.7625 | 477.3462 | −0.77 | 1.19 × 10−25 | 1.97 × 10−24 | −5.9980 | 1.8726 | Lipids and lipid-like molecules | Glycerophospholipids | Phosphatidylserines |
Benign vs. Malignant (borderline + malignant) (Plasma) | ||||||||||
5′-O-Methylmelledonal | 1.5925 | 485.158 | 3.19 | 0.0248 | 0.3291 | −0.3308 | 1.4676 | Lipids and lipid-like molecules | Prenol lipids | Melleolides and analogues |
Tryptophyl-Tyrosine | 2.3507 | 409.1868 | 0.15 | 0.0146 | 0.2873 | −0.2541 | 2.0151 | Organic acids and derivatives | Carboxylic acids and derivatives | Dipeptides |
3,4-Dihydroxymandelic acid | 3.7132 | 185.0443 | 0.29 | 0.0360 | 0.3513 | −0.5068 | 1.5459 | Benzenoids | Phenols | Catechols |
Lucidenic acid A | 4.9003 | 476.306 | 12.25 | 0.0139 | 0.2868 | 1.1363 | 1.4422 | Lipids and lipid-like molecules | Prenol lipids | Triterpenoids |
2-trans,4-cis-Decadienoyl carnitine | 7.0519 | 312.2159 | 0.45 | 0.0126 | 0.2780 | 0.4928 | 1.1053 | Lipids and lipid-like molecules | Fatty Acyls | 0 |
Borderline vs. Malignant (Urine) | ||||||||||
16a-Hydroxyestrone | 5.0385 | 269.1495 | −13.21 | 0.0127 | 0.6276 | −0.7163 | 2.1758 | Lipids and lipid-like molecules | Steroids and steroid derivatives | Estrogens and derivatives |
Coniferyl alcohol | 5.2862 | 181.0855 | 4.04 | 0.0123 | 0.6276 | −0.7280 | 2.2225 | Benzenoids | Phenols | Methoxyphenols |
Indoleacrylic acid | 5.4391 | 171.0637 | 3.20 | 0.0286 | 0.6276 | −0.4444 | 1.5046 | Organoheterocyclic compounds | Indoles and derivatives | Indoles |
(E)-Casimiroedine | 6.0093 | 436.2202 | −1.56 | 0.0008 | 0.6276 | −0.5977 | 2.1053 | Phenylpropanoids and polyketides | Cinnamic acids and derivatives | Glycosylamines |
Cerulenin | 7.2691 | 224.1282 | 6.21 | 0.0132 | 0.6276 | −0.5413 | 1.6339 | Organoheterocyclic compounds | Epoxides | Oxirane carboxylic acids and derivatives |
Heading | Discovery Set | Validation Set | |||||
---|---|---|---|---|---|---|---|
AUC | Cutoff | Sensitivity | Specificity | AUC | Sensitivity | Specificity | |
Normal vs. Ovarian tumor (Urine) | |||||||
2-Meta | 0.987 | 0.855 | 94.26% | 95.00% | 0.984 | 97.66% | 87.50% |
CA125 | 0.965 | 14.78 | 87.70% | 95.00% | 0.978 | 89.84% | 95.00% |
Benign vs. Malignant (borderline + malignant) (Plasma) | |||||||
5-Meta | 0.876 | 0.72 | 87.36% | 62.86% | 0.896 | 86.36% | 78.57% |
CA125 | 0.882 | 35 | 88.51% | 65.71% | 0.903 | 86.36% | 71.43% |
5-Meta + CA125 | 0.972 | 0.71 | 93.10% | 91.43% | 0.932 | 90.91% | 92.86% |
Borderline vs. Malignant (Urine) | |||||||
5-Meta | 0.943 | 0.828 | 98.65% | 84.62% | 0.836 | 80.26% | 71.43% |
CA125 | 0.830 | 165.5 | 81.08% | 76.92% | 0.807 | 80.26% | 42.86% |
Heading | Discovery Set | Validation Set | |||||
---|---|---|---|---|---|---|---|
AUC | Cutoff | Sensitivity | Specificity | AUC | Sensitivity | Specificity | |
Benign vs. Malignant (borderline + malignant) (Plasma) | |||||||
5-Meta | 0.847 | 0.72 | 80.77% | 62.86% | 0.988 | 100% | 78.57% |
CA125 | 0.733 | 35 | 69.23% | 65.71% | 0.893 | 83.33% | 71.43% |
5-Meta + CA125 | 0.922 | 0.71 | 80.77% | 91.43% | 1 | 100% | 92.86% |
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Liu, X.; Liu, G.; Chen, L.; Liu, F.; Zhang, X.; Liu, D.; Liu, X.; Cheng, X.; Liu, L. Untargeted Metabolomic Characterization of Ovarian Tumors. Cancers 2020, 12, 3642. https://doi.org/10.3390/cancers12123642
Liu X, Liu G, Chen L, Liu F, Zhang X, Liu D, Liu X, Cheng X, Liu L. Untargeted Metabolomic Characterization of Ovarian Tumors. Cancers. 2020; 12(12):3642. https://doi.org/10.3390/cancers12123642
Chicago/Turabian StyleLiu, Xiaona, Gang Liu, Lihua Chen, Fei Liu, Xiaozhe Zhang, Dan Liu, Xinxin Liu, Xi Cheng, and Lei Liu. 2020. "Untargeted Metabolomic Characterization of Ovarian Tumors" Cancers 12, no. 12: 3642. https://doi.org/10.3390/cancers12123642