Vitronectin Levels in the Plasma of Neuroblastoma Patients and Culture Media of 3D Models: A Prognostic Circulating Biomarker?
Abstract
:1. Introduction
2. Results
2.1. Higher VN Release in 3D Models
2.2. VN Secretion Independent of Cell Numbers
2.3. Clinical and Genetic Characteristics of NB Patients Included in This Study
2.4. Discriminatory Power of Plasma VN Levels for NB Patient Outcomes
2.5. Plasma VN Level Association with Stage and Genetic Features of NB
3. Discussion
4. Materials and Methods
4.1. Two-Dimensional Cell Cultures
4.2. Three-Dimensional Hydrogel Construction
4.3. Patients and Samples
4.4. Plasma VN Determination
4.5. Statistical Analysis
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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Total Cohort | VN > 361 µg/mL | VN < 361 µg/mL | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Mean ± SD | N | % | Mean ± SD | N | % | Mean ± SD | N | % | ||
Total | 114 | 100% | 24 | 21% | 90 | 79% | ||||
OS | Dead | 65.1 ± 37.8 | 33 | 29% | 53.4 ± 31.0 | 14 | 58% | 68.3 ± 38.9 | 19 | 21% |
Alive | 81 | 71% | 10 | 42% | 71 | 79% | ||||
EFS | Event | 52.7 ± 39.7 | 46 | 40% | 46.0 ± 53.4 | 14 | 58% | 54.5 ± 40.6 | 32 | 36% |
Non-event | 68 | 60% | 10 | 42% | 58 | 64% | ||||
Age | >18 months | 27.2 ± 35.2 | 52 | 46% | 39.4 ± 57.7 | 14 | 27% | 23.9 ± 25.2 | 38 | 73% |
≤18 months | 62 | 54% | 10 | 16% | 52 | 84% | ||||
Stage | Stage 4 | 54 | 47% | 15 | 63% | 39 | 43% | |||
Non-stage 4 | 58 | 51% | 9 | 38% | 51 | 57% | ||||
Unknown | 2 | 2% | 2 | 8% | 0 | 0% | ||||
MYCNStatus | Amplified | 20 | 18% | 6 | 25% | 14 | 16% | |||
Het-amplified | 4 | 4% | 0 | 0% | 4 | 4% | ||||
Non-amplified | 90 | 79% | 18 | 75% | 72 | 80% | ||||
Chromosomic profile | Typical SCA | 60 | 53% | 17 | 71% | 43 | 48% | |||
Atypical SCA | 2 | 2% | 1 | 4% | 1 | 1% | ||||
NCA | 33 | 29% | 3 | 13% | 30 | 33% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% | ||||
−1p | Present | 29 | 25% | 8 | 33% | 21 | 23% | |||
Absent | 66 | 58% | 13 | 54% | 53 | 59% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% | ||||
+1q | Present | 9 | 8% | 3 | 13% | 6 | 7% | |||
Absent | 86 | 75% | 18 | 75% | 68 | 76% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% | ||||
+2p | Present | 23 | 20% | 7 | 29% | 16 | 18% | |||
Absent | 72 | 63% | 14 | 58% | 58 | 64% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% | ||||
−3p | Present | 13 | 11% | 5 | 21% | 8 | 9% | |||
Absent | 82 | 72% | 16 | 67% | 66 | 73% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% | ||||
−4p | Present | 10 | 9% | 2 | 8% | 8 | 9% | |||
Absent | 85 | 75% | 19 | 79% | 66 | 73% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% | ||||
−11q | Present | 29 | 25% | 12 | 50% | 17 | 19% | |||
Absent | 66 | 58% | 9 | 38% | 57 | 63% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% | ||||
−17q | Present | 49 | 43% | 14 | 58% | 35 | 39% | |||
Absent | 46 | 40% | 7 | 29% | 39 | 43% | ||||
Unknown | 19 | 17% | 3 | 13% | 16 | 18% |
Correlation of Clinic-Molecular Features of NB Patients Older than 18 Months and VN Levels | ||||
---|---|---|---|---|
Plasma VN Levels | Spearman r (95% CI) | p-Value (Two-Tailed) | ||
>361 µg/mL | <361 µg/mL | |||
Death (yes/no) | 13/1 | 16/22 | 0.363 (0.186–0.517) | 0.000 * |
Relapse (yes/no) | 13/1 | 18/20 | 0.179 (−0.010–0.356) | 0.1572 |
Unknown/metastatic/localized | 1/10/3 | 23/15 | 0.217 (0.003–0.392) | 0.021 * |
MYCN status (MNA/MNNA) | 4/10 | 11/27 | 0.115 (−0.077–0.298) | 0.226 |
Genomic profile (unknow/SCAs/NCAs) | 2/12/0 | 6/29/3 | 0.248 (0.046–0.430) | 0.014 * |
−1p (unknown/present/absent) | 2/6/6 | 7/17/14 | 0.157 (−0.050–0.351) | 0.125 |
+1q (unknown/present/absent) | 2/2/10 | 8/6/24 | −0,005 (−0.211–0.201) | 0.959 |
+2p (unknown/present/absent) | 2/5/7 | 7/11/20 | 0.138 (−0.073–0.330) | 0.192 |
−3p (unknown/present/absent) | 2/4/8 | 8/7/23 | 0.126 (−0.083–0.324) | 0.222 |
−4p (unknown/present/absent) | 2/2/10 | 8/7/23 | −0.024 (−0.229 to 0.183) | 0.819 |
−11q (unknown/present/absent) | 2/9/3 | 7/16/15 | 0.277 (0.076–0.456) | 0.006 * |
+17q (unknown/present/absent) | 2/9/3 | 8/22/8 | 0.176 (−0.032–0.369) | 0.087 |
Variable | B | SE | Wald | Exp (B) | p-Value |
---|---|---|---|---|---|
OS Wald (forward stepwise) method | |||||
VN cutoff | 1.329 | 0.447 | 8.844 | 3.778 | 0.003 * |
OS Wald (backward stepwise) method | |||||
VN cutoff | 1.263 | 0.449 | 7.922 | 3.536 | 0.005 * |
MYCN status | 0.840 | 0.460 | 3.335 | 2.316 | 0.068 |
EFS Wald (forward stepwise) method | |||||
−4p | −1.471 | 0.752 | 3.825 | 0.230 | 0.050 |
VN cutoff | 1.460 | 0.472 | 9.575 | 4.307 | 0.002 * |
EFS Wald (backward stepwise) method | |||||
−4p | −1.471 | 0.752 | 3.825 | 0.230 | 0.050 |
VN cutoff | 1.460 | 0.472 | 9.575 | 4.307 | 0.002 * |
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López-Carrasco, A.; Vieco-Martí, I.; Granados-Aparici, S.; Acevedo-León, D.; Estañ-Capell, N.; Portugal, R.; Huerta-Aragonés, J.; Cañete, A.; Navarro, S.; Noguera, R. Vitronectin Levels in the Plasma of Neuroblastoma Patients and Culture Media of 3D Models: A Prognostic Circulating Biomarker? Int. J. Mol. Sci. 2024, 25, 8733. https://doi.org/10.3390/ijms25168733
López-Carrasco A, Vieco-Martí I, Granados-Aparici S, Acevedo-León D, Estañ-Capell N, Portugal R, Huerta-Aragonés J, Cañete A, Navarro S, Noguera R. Vitronectin Levels in the Plasma of Neuroblastoma Patients and Culture Media of 3D Models: A Prognostic Circulating Biomarker? International Journal of Molecular Sciences. 2024; 25(16):8733. https://doi.org/10.3390/ijms25168733
Chicago/Turabian StyleLópez-Carrasco, Amparo, Isaac Vieco-Martí, Sofía Granados-Aparici, Delia Acevedo-León, Nuria Estañ-Capell, Raquel Portugal, Jorge Huerta-Aragonés, Adela Cañete, Samuel Navarro, and Rosa Noguera. 2024. "Vitronectin Levels in the Plasma of Neuroblastoma Patients and Culture Media of 3D Models: A Prognostic Circulating Biomarker?" International Journal of Molecular Sciences 25, no. 16: 8733. https://doi.org/10.3390/ijms25168733