Kynureninase Promotes Immunosuppression and Predicts Survival in Glioma Patients: In Silico Data Analyses of the Chinese Glioma Genome Atlas (CGGA) and of the Cancer Genome Atlas (TCGA)

Author:

Pérez de la Cruz Gonzalo1,Pérez de la Cruz Verónica2ORCID,Navarro Cossio Javier3,Vázquez Cervantes Gustavo Ignacio2ORCID,Salazar Aleli3ORCID,Orozco Morales Mario3,Pineda Benjamin3ORCID

Affiliation:

1. Department of Mathematics, Faculty of Sciences, Universidad Nacional Autónoma de México, UNAM, Mexico City 04510, Mexico

2. Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico

3. Neuroimmunology Unit, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City 14269, Mexico

Abstract

Kynureninase (KYNU) is a kynurenine pathway (KP) enzyme that produces metabolites with immunomodulatory properties. In recent years, overactivation of KP has been associated with poor prognosis of several types of cancer, in particular by promoting the invasion, metastasis, and chemoresistance of cancer cells. However, the role of KYNU in gliomas remains to be explored. In this study, we used the available data from TCGA, CGGA and GTEx projects to analyze KYNU expression in gliomas and healthy tissue, as well as the potential contribution of KYNU in the tumor immune infiltrate. In addition, immune-related genes were screened with KYNU expression. KYNU expression correlated with the increased malignancy of astrocytic tumors. Survival analysis in primary astrocytomas showed that KYNU expression correlated with poor prognosis. Additionally, KYNU expression correlated positively with several genes related to an immunosuppressive microenvironment and with the characteristic immune tumor infiltrate. These findings indicate that KYNU could be a potential therapeutic target for modulating the tumor microenvironment and enhancing an effective antitumor immune response.

Funder

Consejo Nacional de Ciencia y Tecnología

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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