Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. The PRISMA Method
2.2. Search Sentence
2.3. Inclusion and Exclusion Criteria
2.4. Meta-Analysis
3. Results
3.1. PRISMA Process
3.2. Characteristics of the Included Studies
Ref. | Kind | Platform | Type of Study | Ethics Approval | Urine Collection | Urine Storage | Analytical Validation | ROC Curve (Training/Testing) |
---|---|---|---|---|---|---|---|---|
[28] | VOL | FAIMS + GC-MS | CRC/control | yes | ND | −80 °C | 1/2–1/2 repeated 5 times | - |
* [35] | MET | GC + LC | CRC/control | yes | Fasting urine | −80 °C | 2/3–1/3 | 0.993 (7 compounds)/0.998 |
[32] | MET | RRLC-TOF/MS | CRC/control | yes | First morning urine | −80 °C | 2/3–1/3 | - |
* [36] | MET | NMR | CRC/control | yes | First morning urine | −80 °C | - | 0.823 taurine, 0.783 alanine, 0.842 3-aminoisobutyrate/ND |
[33] | MET | LC-FAIMS-MS | CRC/control | yes with ID | ND | −80 °C | - | 0.71/ND |
* [25] | MET | Targeted LC-MS/MS | CRC/control | yes with ID | Controls at 7–8 a.m., 11–12 a.m., and 5–6 p.m. CRC at 9 a.m. and 4 p.m. | −80 °C | bootstrapping with virtual datasets | 0.794/ND |
[31] | MET | CE-MS | CRC/control (including stages) | yes | Morning urine | −80 °C | - | 0.906/ND |
* [24] | MET | Targeted LC-MS/MS | CRC/control (including stages) | yes with ID | ND | −80 °C | yes | 0.903/0.872 |
* [37] | MET | 1H-NMR | CRC/control (including stages + other cancers) | yes | Fasting morning urine | −80 °C | 80% training, 20% testing | 0.875 alanine, 0.913 glutamine, 0.933 aspartic acid/ND |
[38] | MET | HPLC-ESI-MS/MS | CRC/control (+ other cancers) | yes | ND | −80 °C | - | - |
[39] | MET | LC-MS/MS MRM | CRC/control (+ other cancers) | yes | First morning urine | −80 °C | - | - |
* [29] | VOL | Needle trap + GC-MS | CRC/control (+ other cancer) | yes | First morning urine | −80 °C | 2/3–1/3 | - |
[40] | VOL | GC-MS | CRC/control (+ other cancers) | yes | ND | ND | - | - |
[41] | VOL | GC-MS | CRC/control (+ other cancers) | yes | Fasting morning urine | −80 °C | - | - |
[30] | VOL | E-nose | CRC/control (+ other diseases) | yes | Fasting morning urine | −80 °C | - | - |
[42] | MET | RP-HPLC | CRC/control (along time) | yes | Spontaneous urine samples 1 day before surgery and day 8 after | −20 °C | - | 0.896 1-methylguanosine, 0.816 pseudouridine/ND |
[22] | MET | UPLC-QTOF-MS | CRC no-relapse/relapse | ND | ND | ND | 2-fold cross-validation with 10,000 validations | AUC: 0.9675 (positive charge) and 0.95 (negative charge)/ND |
* [43] | MET | GC-MS | CRC/control (pre-/post-surgery) | yes | Fasting morning urine | −80 °C | 16/17–1/17 | - |
* [44] | MET | 1H-NMR + GC-MS | CRC pre-/post-surgery and 6-/12-months follow-up AND intra-stages | yes | Pre-/post-surgery overnight fasting urine, 6-/12-months follow-up URINE spot | −80 °C | - | 0.89 (20 compounds)/ND |
[45] | MET | UPLC-MS | CRC/control (pre-/post-surgery + along time) | yes | Fasting urine (7:00 a.m.) | −80 °C | - | - |
[26] | MET | targeted HPLC/GC-MS | CRC/adenoma/control | yes | Spot sample before surgery | ND | - | 0.690 8-oxoGua, 0.635 8-oxoGuo, 0.669 5-hmUra/ND |
[46] | MET | UPLC-MS/HPLC-MS | CRC/adenoma/control | yes | Morning fasting urine | −80 °C | 7-fold | 0.959 (12 compounds), 0.894 (7 nucleotides)/ND |
[47] | MET | HPLC-MS/MS | CRC/adenoma/control | ND | Spot urine | −20 °C | - | - |
[48] | VOL | FAIMS + GC-IMS | CRC/ adenoma/control (+ other diseases) | yes | ND | −80 °C | - | 0.98/ND |
[49] | VOL | FAIMS | CRC/adenoma/control (+ other cancers and diseases) | yes | Spot urine | −80 °C | - | 0.9/ND |
[23] | MET | NMR + targeted LC-MS/MS | Adenoma/control | yes with ID | Midstream urine | −80 °C ǂ | 2/3–1/3 | 0.687/0.692 |
[27] | MET | 1D NMR | Adenoma/control | yes | Midstream urine | 4 h at 4 °C 24 h at −80 °C | Validation of Deng L 2017 | 0.717/ND |
* [50] | MET | 1D NMR | Adenoma/control | yes | Midstream urine | 4 h at 4 °C 24 h at −80 °C | 2/3–1/3 | 0.752/ND |
Ref. (Kind) | Group | N | Age (Error and Type) | Male/Female | Cancer Staging Classification (n) | Country |
---|---|---|---|---|---|---|
[28] | CRC | 83 | 60 (ND: 17) | 53/30 | ND | UK |
(VOL) | Control | 50 | 47 (ND: 16) | 21/29 | - | |
* [35] | CRC | 101 | 60 (R: 24–83) | 58/43 | 0 (0), I (24), II (45), III (27), IV (5) | CN |
(MET) | Control | 103 | 58 (R: 31–76) | 31/72 | ||
[32] | CRC | 29 | ND | - | ND | CN |
(MET) | Control | 10 | ND | - | - | |
* [36] | CRC | 92 | 60 (R: 32–85) | 62/30 | 0 (24), I (8), II (7), III (13), IV (4) | KR |
(MET) | Control | 156 | 52 (R: 22–76) | 76/80 | ||
[33] | CRC | 56 | 65.4 (SD: 11.5) | 33/23 | A (8), B (17), C1 (20), C2 (9) | UK |
(MET) | Control (spouse) | 45 | 60.7 (SD: 12.1) | 15/30 | - | |
Control (relative) | 37 | 50 (SD: 14.1) | 17/20 | - | ||
* [25] | CRC-Malignant | 201 | 68.7 (ND: 0.8) | 114/87 | 0 (3), I/II (103), III (88), IV (7) | JP |
(MET) | CRC-Benign | 14 | 65 (ND: 3.1) | 11/3 | - | |
Control | 17 | 42.1 (ND: 2.8) | 13/4 | - | ||
[31] | CRC | 20 | 73 (ND) | 10/10 | I/II (8), III/IV (12) | CN |
(MET) | Control | 14 | 68 (ND) | 8/6 | - | |
* [24] | CRC-CAD | 121 | 67.4 (ND: 10.9) | 68/59 | 0 (3); I (16), II (30), III (51), IV (21) | CA/US |
(MET) | CRC-MSKCC | 50 | 63.8 (ND: 12.5) | 24/26 | 0 (0), I (14), II (20), III (6), IV (10) | |
Control | 171 | 58.9 (ND: 5.6) | 100/71 | - | ||
* [37] | CRC | 55 | 60 (ND) | 26/29 | I/II (23), III/IV (32) | CN |
(MET) | Control | 40 | 59 (ND) | 19/21 | - | |
EC | 18 | 61 (ND) | 8/10 | - | ||
[38] | CRC | 26 | 65.3 (R: 33–88) | 12/24 | 0 (0), I (3), II (6), III (10), IV (7) | TW |
(MET) | Control | 45 | ND | - | - | |
LC | 27 | 60.8 (R: 42–81) | 16/11 | - | ||
GC | 15 | 67.1 (R: 50–82) | 12/3 | - | ||
BC | 36 | ND | - | - | ||
[39] | CRC | 10 | 51.5 (SD: 6.6) | 5/5 | ND | CN |
(MET) | Control | 10 | 48.7 (SD: 6.43) | 5/5 | - | |
LC | 10 | 52.5 (SD: 7.47) | 5/5 | - | ||
NpC | 10 | 49.3 (SD: 9.09) | 5/5 | - | ||
* [29] | CRC | 30 | ND (R: 45–83) | 16/14 | ND | PT |
(VOL) | Control | 30 | ND (R: 18–78) | 14/16 | - | |
BC | 30 | ND (R: 38–83) | 0/30 | - | ||
[40] | CRC | 8 | ND | - | ND | ND |
(VOL) | Control | 35 | ND | - | - | |
LC | 14 | ND | - | - | ||
EC | 12 | ND | - | - | ||
GC | 12 | ND | - | - | ||
[41] | CRC | 11 | 62 (SD: 12.4 R: 49–78) | 8/3 | ND | PT |
(VOL) | Control | 21 | 62 (SD: 10.3 R: 28–60) | 18/3 | - | |
LeukC | 14 | 50.1 (SD: 12.4 R: 40–74) | 6/8 | - | ||
LyC | 7 | 42 (SD: 19.1 R: 18–68) | 6/1 | - | ||
[30] | CRC | 39 | 70 (ND) | 28/11 | ND | UK |
(VOL) | Control | 18 | 41 (ND) | 13/5 | - | |
IBS | 35 | 48 (ND) | 4/31 | - | ||
[42] | CRC | 52 | 63 (R: 26–87) | 27/25 | A (5), B (22), C (18), D (7) | CN |
(MET) | Control | 62 | 59 (R: 24–78) | 33/29 | - | |
[22] | CRC non-relapse | 20 | ND | - | ND | |
(MET) | CRC relapse | 20 | ND | - | ND | |
* [43] | CRC | 60 | 58.8 (ND) | 34/26 | 0 (0), I (7), II (23), III (21), IV (9) | CN |
(MET) | Control | 63 | 55.5 (ND) | 32/31 | - | |
* [44] | CRC pre-S | 97 | 64.8 (SD: 12.9) | 59/38 | 0 (5), I (12), II (40), III (22), IV (18) | DE |
(MET) | CRC post-S | 12 | 63.9 (SD: 12.5) | 10/2 | 0 (0), I (4), II (4), III (2), IV (2) | |
CRC (6 m) | 52 | 60.1 (SD: 11) | 38/14 | 0 (0), I (12), II (17), III (15), IV (8) | ||
CRC (12 m) | 38 | 61.5 (SD: 11.6) | 24/14 | 0 (0), I (7), II (13), III (14), IV (4) | ||
[45] | CRC | 24 | 65.03 (SD: 10.43) | 13/11 | A (1), B (1), C (12), D (0) | CN |
(MET) | Control | 80 | 64 (SD: 9.87) | 43/37 | - | |
[26] | Adenoma | 15 | 66 (ND) | 8/7 | - | PL |
(MET) | CRC | 72 | 54 (ND) | 31/41 | ND | |
Control | 56 | 65 (ND) | 32/24 | - | ||
[46] | CRC-Malignant | 94 | ND | - | ND | CN |
(MET) | Control | 34 | ND | - | - | |
[47] | Adenoma | 10 | ND | - | - | CN |
(MET) | CRC | 52 | 60 (R: 26–87) | 29/23 | A (7), B (23), C (15), D (7) | |
Control | 60 | 52 (R: 21–71) | 31/39 | - | ||
[48] | Adenoma | 80 | 67 (ND)ǂ | 93/70ǂ | - | UK |
(VOL) | CRC | 12 | ND | |||
Control | 83 | - | ||||
Other (DD, Hemorrhoids, etc.) | 33 | - | ||||
[49] | Adenoma | 94 | 68 (R: 29–89) ǂ | 286/276 ǂ | - | UK |
(VOL) | High risk adenoma | 27 | - | |||
CRC | 35 | ND | ||||
Control | 233 | - | ||||
Others (DD, IBD, MC, etc.,) | 173 | - | ||||
[23] | Adenoma | 155 | 59.9 (SD: 7.4) | 95/60 | ND | CA |
(MET) | Control | 530 | 56.1 (SD: 8.2) | 222/308 | - | |
[27] | Adenoma | 345 | 65.1 (SEM: 6.6) | 197/148 | ND | CN |
(MET) | Control | 316 | 61.8 (SEM: 7.4) | 82/234 | - | |
* [50] | Adenoma | 243 | 59.5 (SEM: 0.67) | 145/98 | ND | CA |
(MET) | Control | 633 | 55.8 (SEM: 0.47) | 269/364 | - |
3.3. Systematic Review
3.4. Quality Assurance
3.5. Meta-Analysis
3.5.1. Vote-Counting Results by Group
Common Name | No. of Cohorts | Behavior (Up-Down-Equal) | Vote-Counting | N | Reference |
---|---|---|---|---|---|
CRC and Advanced Adenoma vs. Control | |||||
N1,N12-Diacetylspermine | 3 | 3–0–0 | 3 | 928 | [24,25] ɫ |
D-Glucose | 2 | 2–0–0 | 2 | 696 | [24] ɫ |
L-Kynurenine | 2 | 2–0–0 | 2 | 696 | [24] ɫ |
L-Proline | 2 | 2–0–0 | 2 | 696 | [24] ɫ |
Creatinine | 2 | 0–2–0 | −2 | 452 | [35,36] |
Phenol | 2 | 0–2–0 | −2 | 294 | [29,35] |
Putrescine | 3 | 2–0–1 | 2 | 900 | [24,35] ɫ |
Hippuric acid | 4 | 0–3–1 | −3 | 1148 | [24,35,36] ɫ |
Indole-3-acetic acid | 3 | 0–2–1 | −2 | 900 | [24,35] ɫ |
Citric acid | 5 | 1–3–1 | −2 | 1271 | [24,35,36,43] ɫ |
P-Cresol | 2 | 1–1–0 | 1 | 417 | [35,43] |
Tetradecenoyl carnitine (C14:1) | 2 | 1–0–1 | 1 | 696 | [24] ɫ |
2-Aminohexanedioic acid | 2 | 0–1–1 | −1 | 696 | [24] ɫ |
3-(3-Hydroxyohenyl)-3-hydroxypropanoic acid | 2 | 0–1–1 | −1 | 696 | [24] ɫ |
Aspartic acid | 2 | 0–1–1 | −1 | 696 | [24] ɫ |
3-Hidroxybutyric acid | 2 | 1–1–0 | 0 | 696 | [24] ɫ |
Butyric acid | 2 | 1–1–0 | 0 | 696 | [24] ɫ |
Hydroxyproline | 2 | 1–1–0 | 0 | 696 | [24] ɫ |
L-Alanine | 2 | 1–1–0 | 0 | 452 | [35,36] |
L-Dopa | 2 | 1–1–0 | 0 | 696 | [24] ɫ |
L-Tryptophan | 2 | 1–1–0 | 0 | 327 | [35,43] |
Urea | 2 | 1–1–0 | 0 | 452 | [35,36] |
CRC Stage vs. Control | |||||
Hippuric acid | 2 | 1–1–0 | 0 | 248 | [37,44] |
Pre-surgery vs. Post-surgery | |||||
Salicyluric acid | 2 | 0–2–0 | −2 | 258 | [43,44] |
Asparagine | 2 | 1–1–0 | 0 | 258 | [43,44] |
Citrate | 2 | 1–1–0 | 0 | 258 | [43,44] |
Tyrosine | 2 | 1–1–0 | 0 | 246 | [43,44] |
3.5.2. Statistical Results by Group
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound Name | Combined and Weighted p-Value | Combined and Weighted Fold-Change | N Total | HMDB ID | Healthy Normal Urine Concentration (Adult > 18 y) (µmol/mmol Creatinine) | CRC Projected Urine Concentration (Adult > 18 y) (µmol/mmol Creatinine) |
---|---|---|---|---|---|---|
3-Hidroxybutyric acid | 1.85 × 10−4 | 17.56 | 342 | HMDB0000357 | 1.4–2.7 | 5.8–11.2 |
L-Dopa | 2.60 × 10−4 | 14.63 | 342 | HMDB0000181 | 0.01–0.04 | 0.04–0.15 |
L-Histidinol | 8.71 × 10−9 | 12.76 | 204 | HMDB0003431 | NQ | - |
N1,N12-Diacetylspermine | 6.00 × 10−14 | 10.75 | 342 | HMDB0002172 | 0–0.0260 | 0–0.280 |
1,1,6-Trimethyl-1,2-dihydronaphthalene | 3.31 × 10−2 | 0.22 | 60 | HMDB0040284 | NQ | - |
Hippuric acid | 2.59 × 10−3 | 0.23 | 546 | HMDB0000714 | 28–610 | 6–140 |
Ether | 1.42 × 10−3 | 0.18 | 60 | - | NQ | - |
Pyruvic acid | 8.82 × 10−8 | 0.09 | 204 | HMDB0000243 | 1–3.7 | 0.09–0.33 |
Butyraldehyde | 5.76 × 10−4 | 0.003 | 60 | HMDB0003543 | NQ | - |
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Mallafré-Muro, C.; Llambrich, M.; Cumeras, R.; Pardo, A.; Brezmes, J.; Marco, S.; Gumà, J. Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis. Cancers 2021, 13, 2534. https://doi.org/10.3390/cancers13112534
Mallafré-Muro C, Llambrich M, Cumeras R, Pardo A, Brezmes J, Marco S, Gumà J. Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis. Cancers. 2021; 13(11):2534. https://doi.org/10.3390/cancers13112534
Chicago/Turabian StyleMallafré-Muro, Celia, Maria Llambrich, Raquel Cumeras, Antonio Pardo, Jesús Brezmes, Santiago Marco, and Josep Gumà. 2021. "Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis" Cancers 13, no. 11: 2534. https://doi.org/10.3390/cancers13112534