Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks
Indoleamine dioxygenase (IDO), a rate limiting enzyme of the tryptophan catabolism through the kynurenine pathway (KP), has been related with a lower survival and a poor patient prognosis on several solid tumors, including gliomas. However, the use of IDO inhibitors as a therapeutic strategy for tum...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/12/11/1054 |
| _version_ | 1797467236131143680 |
|---|---|
| author | Gustavo Ignacio Vázquez Cervantes Javier Ángel Navarro Cossio Gonzalo Pérez de la Cruz Aleli Salazar Verónica Pérez de la Cruz Benjamin Pineda |
| author_facet | Gustavo Ignacio Vázquez Cervantes Javier Ángel Navarro Cossio Gonzalo Pérez de la Cruz Aleli Salazar Verónica Pérez de la Cruz Benjamin Pineda |
| author_sort | Gustavo Ignacio Vázquez Cervantes |
| collection | DOAJ |
| description | Indoleamine dioxygenase (IDO), a rate limiting enzyme of the tryptophan catabolism through the kynurenine pathway (KP), has been related with a lower survival and a poor patient prognosis on several solid tumors, including gliomas. However, the use of IDO inhibitors as a therapeutic strategy for tumor treatment remains controversial in clinical trials and the role of other KP enzymes on tumor progression has remained poorly understood so far. Recently, different studies on different types of cancer have pointed out the importance of KP enzymes downstream IDO. Because of this, we conducted a bioinformatic analysis of the expression of different KP enzymes and their correlation with the gene expression of molecules related to the hallmarks of cancer in transcriptomic datasets from patients with different types of brain tumors including low grade gliomas, glioblastoma multiforme, neuroblastoma, and paraganglioma and pheochromocytoma. We found that KP enzymes that drive to NAD+ synthesis are overexpressed on different brain tumors compared to brain cortex data. Moreover, these enzymes presented positive correlations with the expression of genes related to immune response modulation, angiogenesis, Signal Transducer and Activator of Transcription (STAT) signaling, and Rho GTPase expression. These correlations suggest the relevance of the expression of the KP enzymes in brain tumor pathogenesis. |
| first_indexed | 2024-03-09T18:50:49Z |
| format | Article |
| id | doaj.art-5639843e41e3481388967fd77ec68ac9 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T18:50:49Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-5639843e41e3481388967fd77ec68ac92023-11-24T05:50:16ZengMDPI AGMetabolites2218-19892022-11-011211105410.3390/metabo12111054Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma HallmarksGustavo Ignacio Vázquez Cervantes0Javier Ángel Navarro Cossio1Gonzalo Pérez de la Cruz2Aleli Salazar3Verónica Pérez de la Cruz4Benjamin Pineda5Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, MexicoNeurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, MexicoDepartment of Mathematics, Faculty of Sciences, Universidad Nacional Autónoma de México, UNAM, Mexico City 04510, MexicoNeuroimmunology Unit, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, MexicoNeurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, MexicoNeuroimmunology Unit, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, MexicoIndoleamine dioxygenase (IDO), a rate limiting enzyme of the tryptophan catabolism through the kynurenine pathway (KP), has been related with a lower survival and a poor patient prognosis on several solid tumors, including gliomas. However, the use of IDO inhibitors as a therapeutic strategy for tumor treatment remains controversial in clinical trials and the role of other KP enzymes on tumor progression has remained poorly understood so far. Recently, different studies on different types of cancer have pointed out the importance of KP enzymes downstream IDO. Because of this, we conducted a bioinformatic analysis of the expression of different KP enzymes and their correlation with the gene expression of molecules related to the hallmarks of cancer in transcriptomic datasets from patients with different types of brain tumors including low grade gliomas, glioblastoma multiforme, neuroblastoma, and paraganglioma and pheochromocytoma. We found that KP enzymes that drive to NAD+ synthesis are overexpressed on different brain tumors compared to brain cortex data. Moreover, these enzymes presented positive correlations with the expression of genes related to immune response modulation, angiogenesis, Signal Transducer and Activator of Transcription (STAT) signaling, and Rho GTPase expression. These correlations suggest the relevance of the expression of the KP enzymes in brain tumor pathogenesis.https://www.mdpi.com/2218-1989/12/11/1054tryptophan catabolismgliomaimmune response |
| spellingShingle | Gustavo Ignacio Vázquez Cervantes Javier Ángel Navarro Cossio Gonzalo Pérez de la Cruz Aleli Salazar Verónica Pérez de la Cruz Benjamin Pineda Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks Metabolites tryptophan catabolism glioma immune response |
| title | Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks |
| title_full | Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks |
| title_fullStr | Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks |
| title_full_unstemmed | Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks |
| title_short | Bioinformatic Analysis of Kynurenine Pathway Enzymes and Their Relationship with Glioma Hallmarks |
| title_sort | bioinformatic analysis of kynurenine pathway enzymes and their relationship with glioma hallmarks |
| topic | tryptophan catabolism glioma immune response |
| url | https://www.mdpi.com/2218-1989/12/11/1054 |
| work_keys_str_mv | AT gustavoignaciovazquezcervantes bioinformaticanalysisofkynureninepathwayenzymesandtheirrelationshipwithgliomahallmarks AT javierangelnavarrocossio bioinformaticanalysisofkynureninepathwayenzymesandtheirrelationshipwithgliomahallmarks AT gonzaloperezdelacruz bioinformaticanalysisofkynureninepathwayenzymesandtheirrelationshipwithgliomahallmarks AT alelisalazar bioinformaticanalysisofkynureninepathwayenzymesandtheirrelationshipwithgliomahallmarks AT veronicaperezdelacruz bioinformaticanalysisofkynureninepathwayenzymesandtheirrelationshipwithgliomahallmarks AT benjaminpineda bioinformaticanalysisofkynureninepathwayenzymesandtheirrelationshipwithgliomahallmarks |