Somatostatin Receptor Splicing Variant sst5TMD4 Overexpression in Glioblastoma Is Associated with Poor Survival, Increased Aggressiveness Features, and Somatostatin Analogs Resistance
Abstract
:1. Introduction
2. Results
2.1. sst5TMD4 Levels Are Significantly Overexpressed in GBM Samples and Associated with Poor Prognosis and Survival Rate in Patients with GBM
2.2. Overexpression of sst5TMD4 Increases Aggressiveness Parameters in GBM Cells
2.3. Overexpression of sst5TMD4 Modulated the Phosphorylation Levels of Different Proteins Associated with Key Oncogenic Pathways in GBM Cells
2.4. Silencing of sst5TMD4 Reduces Aggressiveness Parameters in GBM Cells
2.5. Overexpression of sst5TMD4 Alters the Basal Expression of SSTR2 in GBM Cells and Sensitized the Response of GBM Cells to Pasireotide Treatment
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Patients and Samples
4.3. Immunohistochemical Analysis
4.4. Cell Cultures
4.5. Modulation of the Levels of sst5TMD4 Expression (Overexpression and Silencing) in GBM Cells
4.6. Measurements of Cell Proliferation
4.7. Measurement of Cell Migration Capacity
4.8. RNA Extraction, Retrotranscription, and Gene Expression Measurement by qPCR
4.9. Human Phosphorylation Pathway Profiling Array
4.10. Bioinformatic and 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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Parameters | Control Patients | Anaplastic Astrocytoma | Glioblastoma |
---|---|---|---|
Patients (n) | 8 | 9 | 47 |
Gender (M/F) | 2(25%)/6(75%) | 3(33.3%)/6(66.7%) | 19(40.4%)/28(59.6%) |
Age at surgical intervention (mean ± desvest) | 44.13 ± 4.32 | 51.9 ± 13.0 | 56.9 ± 13.2 |
% Ki67 (mean ± desvest) | - | 15.2 ± 3.2% | 28 ± 14.6% |
% of TP53 positive | - | 87.5% | 81.8% |
% of IDH1 positive | - | 33% | 11.6% |
% of recurrent tumors | - | 0% | 18% |
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Fuentes-Fayos, A.C.; G-García, M.E.; Pérez-Gómez, J.M.; Peel, A.; Blanco-Acevedo, C.; Solivera, J.; Ibáñez-Costa, A.; Gahete, M.D.; Castaño, J.P.; Luque, R.M. Somatostatin Receptor Splicing Variant sst5TMD4 Overexpression in Glioblastoma Is Associated with Poor Survival, Increased Aggressiveness Features, and Somatostatin Analogs Resistance. Int. J. Mol. Sci. 2022, 23, 1143. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031143
Fuentes-Fayos AC, G-García ME, Pérez-Gómez JM, Peel A, Blanco-Acevedo C, Solivera J, Ibáñez-Costa A, Gahete MD, Castaño JP, Luque RM. Somatostatin Receptor Splicing Variant sst5TMD4 Overexpression in Glioblastoma Is Associated with Poor Survival, Increased Aggressiveness Features, and Somatostatin Analogs Resistance. International Journal of Molecular Sciences. 2022; 23(3):1143. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031143
Chicago/Turabian StyleFuentes-Fayos, Antonio C., Miguel E. G-García, Jesús M. Pérez-Gómez, Annabel Peel, Cristóbal Blanco-Acevedo, Juan Solivera, Alejandro Ibáñez-Costa, Manuel D. Gahete, Justo P. Castaño, and Raúl M. Luque. 2022. "Somatostatin Receptor Splicing Variant sst5TMD4 Overexpression in Glioblastoma Is Associated with Poor Survival, Increased Aggressiveness Features, and Somatostatin Analogs Resistance" International Journal of Molecular Sciences 23, no. 3: 1143. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031143