Features of Metabolites and Biomarkers in Inflammatory and Infectious Complications of Childhood Cancers
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
- Patients less than 18 years old.
- Pediatric patients with cancer.
- Risk of infectious complications (immunosuppression, neutropenia, surgical interventions).
- Patients over 18 years old.
- No risk of infectious complications according to clinical and laboratory data.
- Terminal stage.
2.2. Patients and Samples
2.3. Methods
2.3.1. Reagents for GC–MS Analysis
2.3.2. GC–MS Analysis
2.3.3. Biomarker Analysis
2.3.4. Statistical Analysis
3. Results
3.1. Metabolic Changes
3.1.1. Metabolites and Biomarkers in Healthy Children, Patients without Complications, and Patients with Complications (SIRS, Sepsis, Septic Shock)
3.1.2. Monitoring Metabolites and Biomarkers in Patients with Complications
3.1.3. Changes in the Metabolomic Profile in Patients with Complications
- Body temperature ≥ 38 °C (febrile) or ≤36 °C (hypothermia).
- Heart rate ≥ 90/min (tachycardia).
- Tachypnea: respiratory rate ≥ 20/min or hyperventilation with blood carbon dioxide ≤ 32 mmHg.
- Leukocytosis (≥12,000/μL) or leukopenia (≤4000/μL) or shift in the leukocyte formula to the left.
3.1.4. ROC Analysis
3.1.5. Metabolomic Profile Changes in Survivors vs. Non-Survivors
4. Discussion
4.1. Metabolites
4.2. Biomarkers
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | Healthy Children (n = 18) | Patients without Complications (n = 40) | Patients with Complications (n = 31) |
---|---|---|---|
Gender, males, n (%) | 9 (50.0%) | 26 (65.0%) | 19 (61.3%) |
Gender, females, n (%) | 9 (50.0%) | 14 (35.0%) | 12 (38.7%) |
Age, years (Me (IQR)) | 13.5 (8.0; 16.0) | 9.0 (4.0; 12.0) | 9.0 (4.0; 15.0) |
Cancer stage, n (%) | - | I-8 (20.0%) II-10 (25.0%) III-9 (22.5%) IV-13 (32.5%) | I-9 (29.0%) II-12 (38.7%) III-5 (16.1%) IV-5 (16.1%) |
Bone marrow transplantation, n (%) | - | 1 (2.5%) | 2 (6.5%) |
Leukemia, n (%) | - | 12 (30.0%) | 14 (45.0%) |
Systemic pathology, n (%) | - | - | Aplasia—15 (48.4%), cardiovascular system—8 (25.8%), digestive—8 (25.8%), respiratory organs—7 (22.6%), kidneys—5 (16.1%), CNS—3 (9.7%), SPON—1 (3.2%), liver—1 (3.2%) |
Complications after treatment, n (%) | - | - | Enterocolitis—8 (25.8%), coagulopathy—5 (16.1%), mucositis—4 (12.9%), stomatitis—4 (12.9%), pleurisy—2 (6.5%), bronchitis—2 (6.5%), hemorrhagic syndrome—1 (3.2%), shock—1 (3.2%), epilepsy—1 (3.2%), pyoderma—1 (3.2%) |
Metabolites, μmol/L/Biomarkers | Healthy Children (n = 18) | Patients without Complications (n = 40) | Patients with Complications (n = 31) | p-Value |
---|---|---|---|---|
PhLA | <0.5 (<0.5; <0.5) | <0.5 (<0.5; <0.5) | <0.5 (<0.5; 0.9) | - |
p-HPhAA | <0.5 (<0.5; <0.5) | <0.5 (<0.5; 0.6) | <0.5 (<0.5; 1.0) | - |
p-HPhLA | 1.4 (1.1; 1.8) | 0.9 (0.7; 1.1) | 1.1 (0.8; 1.7) | <0.001 |
Σ3AMM | 2.2 (1.5; 2.6) | 1.5 (1.1; 1.8) | 2.0 (1.6; 3.3) | 0.001 |
Succinic acid | 3.4 (2.7; 4.8) | 2.8 (2.5; 3.6) | 1.9 (1.3; 3.1) | <0.001 |
Fumaric acid | 1.1 (0.9; 1.2) | 0.7 (0.6; 0.9) | 0.8 (0.4; 1.2) | 0.002 |
CRP (mg/L) | 0.3 (0.2; 3.8) | 1.35 (0.9; 2.4) | 128 (66; 201) | <0.001 |
PCT (ng/mL) | 0.06 (0.03; 0.07) | 0.07 (0.05; 0.12) | 4.2 (0.6; 11.8) | <0.001 |
PSP (pg/mL) | 93 (72; 111) | 108 (91; 122) | 526 (331; 917) | <0.001 |
Metabolites, μmol/L/Biomarkers | Patient Point 1 (n = 31) | Patient Point 2 (n = 31) | Patient Point 3 (n = 31) | p-Value |
---|---|---|---|---|
PhLA | <0.5 (<0.5; 0.9) | <0.5 (<0.5; 0.7) | <0.5 (<0.5; <0.5) | - |
p-HPhAA | <0.5 (<0.5; 1) | <0.5 (<0.5; 0.9) | <0.5 (<0.5; 0.5) | - |
p-HPhLA | 1.1 (0.8; 1.7) | 1.0 (0.8; 1.5) | 1.1 (0.8; 1.4) | 0.411 |
Succinic acid | 1.9 (1.3; 3.1) | 2.0 (1.2; 2.9) | 1.6 (1.3; 2.7) | 0.949 |
Fumaric acid | 0.8 (<0.5; 1.2) | 0.7 (<0.5; 1.3) | 0.6 (0.5; 1.4) | 0.841 |
CRP (mg/L) | 128 (66; 201) | 89 (40; 128) | 52 (13; 98) | 0.013 |
PCT (ng/mL) | 5.24 (3; 16.2) | 4.2 (1; 13.1) | 2.6 (0.9; 6.8) | 0.003 |
PSP (pg/mL) | 526 (331; 917) | 517 (213; 941) | 483 (278; 685) | 0.034 |
Metabolites, μmol/L/Biomarkers | Patients with Sepsis/Septic Shock (n = 24) | Patients with Inflammation (n = 7) | p-Value |
---|---|---|---|
Point 1 | |||
PhLA | <0.5 (<0.5; 0.9) | 0.5 (<0.5; 0.7) | 0.872 |
p-HPhAA | <0.5 (<0.5; 0.9) | 0.6 (<0.5; 1.0) | 0.216 |
p-HPhLA | 1.1 (0.9; 1.7) | 1.3 (0.8; 1.7) | 0.729 |
Σ3AMM | 1.7 (1.4; 3.5) | 2.3 (2.1; 2.9) | 0.274 |
Succinic acid | 2.0 (1.3; 2.8) | 1.8 (1.4; 3.1) | 0.908 |
Fumaric acid | 0.7 (<0.5; 1.2) | 0.8 (0.5; 1.2) | 0.945 |
CRP (mg/L) | 147 (67; 202) | 119 (64; 128) | 0.234 |
PCT (ng/mL) | 5.3 (3.2; 17.3) | 0.45 (0.28; 0.88) | 0.003 |
PSP (pg/mL) | 662 (416; 940) | 316 (179; 526) | 0.029 |
Metabolites, μmol/L/Biomarkers | Patients Who Survived (n = 28) | Non-Survivor Patients (n = 3) | p-Value |
---|---|---|---|
PhLA | <0.5 (<0.5; 0.7) | 1.4 (0.6; 3.7) | - |
p-HPhAA | <0.5 (<0.5; 0.9) | 1.02 (<0.5; 1.59) | - |
p-HPhLA | 1.1 (0.8; 1.4) | 2.1 (1.9; 10.6) | 0.007 |
Σ3AMM | 1.9 (1.5; 2.8) | 3.5 (3.5; 15.8) | 0.018 |
Succinic acid | 1.8 (1.3; 2.4) | 3.1 (2.4; 3.6) | 0.065 |
Fumaric acid | 0.7 (0.4; 1.2) | 1.1 (0.6; 1.7) | 0.385 |
CRP (mg/L) | 120 (65; 185) | 239 (174; 317) | 0.030 |
PCT (ng/mL) | 4.1 (0.5; 11.8) | 6.9 (0.7; 161) | 0.663 |
PSP (pg/mL) | 474 (324; 740) | 942 (938; 2331) | 0.024 |
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Getsina, M.; Chernevskaya, E.; Beloborodova, N.; Golovnya, E.; Polyakov, P.; Kushlinskii, N. Features of Metabolites and Biomarkers in Inflammatory and Infectious Complications of Childhood Cancers. Biomedicines 2024, 12, 2101. https://doi.org/10.3390/biomedicines12092101
Getsina M, Chernevskaya E, Beloborodova N, Golovnya E, Polyakov P, Kushlinskii N. Features of Metabolites and Biomarkers in Inflammatory and Infectious Complications of Childhood Cancers. Biomedicines. 2024; 12(9):2101. https://doi.org/10.3390/biomedicines12092101
Chicago/Turabian StyleGetsina, Maria, Ekaterina Chernevskaya, Natalia Beloborodova, Evgeniy Golovnya, Petr Polyakov, and Nicolai Kushlinskii. 2024. "Features of Metabolites and Biomarkers in Inflammatory and Infectious Complications of Childhood Cancers" Biomedicines 12, no. 9: 2101. https://doi.org/10.3390/biomedicines12092101
APA StyleGetsina, M., Chernevskaya, E., Beloborodova, N., Golovnya, E., Polyakov, P., & Kushlinskii, N. (2024). Features of Metabolites and Biomarkers in Inflammatory and Infectious Complications of Childhood Cancers. Biomedicines, 12(9), 2101. https://doi.org/10.3390/biomedicines12092101