Producción CyT
Book of Abstracts XIII CAB2C / 1a ed ampliada. - Ciudad Autónoma de Buenos Aires: A2B2C, 2023. - RIPK1 as a potential therapeutic target against Diffuse Gliomas
Congreso
Autoría:
Amorós Morales, Leslie C. ; Gómez Bergna, Santiago Manuel ; Marchesini, Abril ; Scalise, María Lujan ; Gonzalez, Nazareno ; Candolfi, Marianela ; Romanowski, Victor ; Pidre, Matías LuisFecha:
2023Editorial y Lugar de Edición:
Asociación Argentina de Bioinformática y Biología Computacional Book of Abstracts Este libro es una obra colectiva de los resúmenes enviados por sus autores y presentados en el 12vo Congreso Argentino de Bioinformática y Biología ComputacionaResumen *
Background Diffuse gliomas (DG) are aggressive brain tumors that can be divided based on the presence of a mutation in the enzyme isocitrate dehydrogenase gene (IDH1). In general, mutated IDH1 (mIDH) correlates with a better prognosis compared with wild type IDH1 (wtIDH1). RIPK1 (receptor-interacting protein kinase 1) is an enzyme involved in several signaling pathways. Although the dysregulation of RIPK1 activity has been linked to various diseases, its involvement in glioma needs further investigation. The aim of this work was to characterize the role of RIPK1 in tumor progression associated pathways of DG through in silico analyzes from patient databases. Results We analyzed public datasets containing clinical, genomic and transcriptomic information from 661 patient samples. For this, two bioinformatic platforms were employed (cBioPortal and Xena). Samples corresponding to DG were filtered, classified by IDH status and divided into two subgroups according to the median value of RIPK1 expression, as required. Clinical and molecular attributes were then evaluated in conditions of high and low mRNA RIPK1 levels. The results showed a lower survival probability in patients belonging to the high RIPK1 expression subgroup compared to those samples with low RIPK1 expression. We also observed a higher expression of RIPK1 in wtIDH samples compared to those with mIDH. In order to further characterize the role of RIPK1 in DG, we performed a Gene Ontology and Pathway Enrichment Analysis using the Xena platform’s differential expression tool. The results showed that RIPK1 is involved in inflammatory and immune responses. Hence, the expression levels of some of the genes involved in the following molecular processes crucial for cancer progression were studied: proliferation, epithelial-mesenchymal transition, immune cell infiltration and cell death pathways. Briefly, the results showed significant differences in genes related to increased cellular dedifferentiation, proinflammatory cell death pathways and tumor infiltrating immune cells gene signatures (Welch´s t-test). Conclusions RIPK1 over-expression is associated with a poor prognosis in DG. This fact, together with our in silico results suggest that RIPK1 may play a crucial role for glioma progression, positioning it as a promising candidate for therapeutic targeting. Información suministrada por el agente en SIGEVAPalabras Clave
Gene expressionDiffuse gliomaRIPK1