microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors
Abstract
:1. Introduction
2. Results
2.1. Clinical Characteristics of the Study Subjects
2.2. miRNA Expression Levels and Risk of Incidental Post-Surgical PE
2.2.1. Glioma
2.2.2. Meningioma
2.3. Markers of Neutrophil Activation and Risk of Incidental Post-Surgical PE
2.3.1. Glioma
2.3.2. Meningioma
3. Discussion
4. Materials and Methods
4.1. Study Subjects
4.2. Blood Collection
4.3. miRNA Studies
4.3.1. RNA Isolation
4.3.2. Quantification of the Expression Level of miRNAs
Screening Stage
Validation Stage
4.3.3. Identification of miRNAs’ Targets
4.4. Quantification of Neutrophil Activation Markers
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinical Characteristic | Glioma Patients (n = 50) | Meningioma Patients (n = 50) |
---|---|---|
PE events, n (%) | 17 (34) | 17 (34) |
Age, y | 61 (51–70) | 64 (50–71) |
Female sex, n (%) | 22 (44) | 33 (66) |
BMI, kg/m2 | 24.7 (22.2–27.4) | 25.9 (21.1–29.7) |
Comorbidities, n (%) Cardiovascular Respiratory Metabolic * Miscellanea † | 20 (40) 1 (2) 8 (16) 5 (10) | 18 (36) 2 (4) 5 (10) 5 (10) |
Pre-operative KPS ≥ 80, n (%) | 47 (94) | 49 (98) |
Post-operative KPS ≥ 80, n (%) | 44 (88) | 47 (94) |
WHO classification, n (%) Grade I Grade II Grade III Grade IV | 0 (--) 6 (12) 8 (16) 36 (72) | 45 (90) 5 (10) 0 (--) 0 (--) |
Tumor location, n (%) Skull base Cerebral convexity-falx Superficial Deep-seated | 0 (--) 0 (--) 12 (24) 38 (76) | 15 (30) 35 (70) 0 (--) 0 (--) |
Tumor dimension, cm3 | 24 (12.3–50.2) | 16 (5,8–35.2) |
Duration of surgery, min | 240 (210–240) | 215 (176.3–277.5) |
Khorana score, n (%) 0 1 | 27 (54) 23 (46) | 40 (80) 10 (20) |
Hemoglobin, g/dL | 13.7 (12.7–14.9) | 12.9 (11.9–13.3) |
WBC, ×103/mmc | 10.04 (6.64–12.10) | 6.10 (4.92–7.69) |
Neutrophils, ×103/mmc | 6.03 (3.99–7.26) | 3.66 (2.95–4.62) |
Platelets, ×103/mmc | 226 (188–248) | 216 (189–278) |
PT ratio | 0.99 (0.93–1.09) | 1.02 (0.97–1.08) |
APTT ratio | 0.81 (0.73–0.89) | 0.94 (0.86–1.01) |
Fibrinogen, mg/dL | 229 (196–279) | 257 (222–304) |
D-dimer, ng/mL | 218 (125–565) | 167 (100–210) |
CRP, mg/L | 0.07 (0.03–0.18) | 0.11 (0.06–0.26) |
eGFR, mL/min/1.73 m3 | 93.6 (79.8–113.9) | 90.8 (78.3–107.6) |
miRNA | Sequence | Standardized OR | Fold-Change |
---|---|---|---|
miR-363-3p | aauugcacgguauccaucugua | 0.85 | −1.79 |
miR-93-3p | acugcugagcuagcacuucccg | 0.91 | −1.75 |
miR-22-5p | aguucuucaguggcaagcuuua | 0.99 | −2.50 |
miR-130b-3p | cagugcaaugaugaaagggcau | 1.08 | 2.78 |
miR-885-5p | uccauuacacuacccugccucu | 0.99 | −2.94 |
miR-451a | aaaccguuaccauuacugaguu | 0.94 | −1.61 |
miR-222-3p | agcuacaucuggcuacugggu | 0.88 | −1.54 |
miR-140-3p | uaccacaggguagaaccacgg | 0.77 | −2.04 |
Complement and Coagulation Cascades Pathway | ||
---|---|---|
miRNA | Predicted Target | Validated Target |
miR-363-3p | C4BPA, CR2, CD55, KNG1 | - |
miR-93-3p | PROS1, TFPI, MASP1, F9, C6, C8B, MBL2 | - |
miR-22-5p | TFPI, F11, C8B | - |
miR-130b-3p | SERPINA1, SERPING1, C3, MBL2, SERPINE1, C8A | F3 |
miR-885-5p | CD59, CFI, KNG1 | - |
miR-451a | - | - |
miR-222-3p | - | - |
miR-140-3p | CD59, SERPINA1, MASP1 | - |
miRNA | Sequence | Fold-Change |
---|---|---|
miR-29a-3p | uagcaccaucugaaaucgguua | 1.57 |
miR-660-5p | uacccauugcauaucggaguug | −1.59 |
miR-331-3p | gccccugggccuauccuagaa | 2.20 |
miR-126-5p | cauuauuacuuuugguacgcg | 1.99 |
miR-23a-3p | aucacauugccagggauuucc | 1.91 |
miR-23b-3p | aucacauugccagggauuaccac | 1.95 |
Complement and Coagulation Cascades Pathway | ||
---|---|---|
miRNA | Predicted Target | Validated Target |
miR-29a-3p | BDKRB1, CR1, KNG1, BDKRB2, C8G | FGA, FGB, FGG |
miR-660-5p | C9, KNG1 | - |
miR-331-3p | C3AR1, CFB, F10, F11, KLKB1, SERPINF2, F7 | - |
miR-126-5p | CR2, F8, F9 | - |
miR-23a-3p | CR1, F11, F2R, F8, MBL2, PLAU, PLAUR, PROS1, C1S, SERPINC1 | - |
miR-23b-3p | CR1, F11, F2R, F8, MBL2, PLAUR, PROS1, C1S, SERPINC1 | PLAU |
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Oto, J.; Plana, E.; Solmoirago, M.J.; Fernández-Pardo, Á.; Hervás, D.; Cana, F.; España, F.; Artoni, A.; Bucciarelli, P.; Carrabba, G.; et al. microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors. Cancers 2020, 12, 1536. https://doi.org/10.3390/cancers12061536
Oto J, Plana E, Solmoirago MJ, Fernández-Pardo Á, Hervás D, Cana F, España F, Artoni A, Bucciarelli P, Carrabba G, et al. microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors. Cancers. 2020; 12(6):1536. https://doi.org/10.3390/cancers12061536
Chicago/Turabian StyleOto, Julia, Emma Plana, María José Solmoirago, Álvaro Fernández-Pardo, David Hervás, Fernando Cana, Francisco España, Andrea Artoni, Paolo Bucciarelli, Giorgio Carrabba, and et al. 2020. "microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors" Cancers 12, no. 6: 1536. https://doi.org/10.3390/cancers12061536