RIPK1 as a potential therapeutic target against Diffuse Gliomas

LESLIE C. AMORÓS MORALES; SANTIAGO M. GÓMEZ BERGNA; ABRIL MARCHESINI; MA. LUJÁN SCALISE; NAZARENO GONZÁLEZ; MARIANELA CANDOLFI; VÍCTOR ROMANOWSKI; MATIAS L. PIDRE

Rosario, Santa Fe

Congreso; 13vo Congreso Argentino de Bioinformática y Biología Computacional; 2023

BackgroundDiffuse gliomas (DG) are aggressive brain tumors that can be divided based on thepresence 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 severalsignaling pathways. Although the dysregulation of RIPK1 activity has been linked to variousdiseases, its involvement in glioma needs further investigation. The aim of this work was tocharacterize the role of RIPK1 in tumor progression associated pathways of DG through insilico analyzes from patient databases.ResultsWe analyzed public datasets containing clinical, genomic and transcriptomic informationfrom 661 patient samples. For this, two bioinformatic platforms were employed (cBioPortaland Xena). Samples corresponding to DG were filtered, classified by IDH status and dividedinto two subgroups according to the median value of RIPK1 expression, as required. Clinicaland molecular attributes were then evaluated in conditions of high and low mRNA RIPK1levels. The results showed a lower survival probability in patients belonging to the highRIPK1 expression subgroup compared to those samples with low RIPK1 expression. Wealso observed a higher expression of RIPK1 in wtIDH samples compared to those withmIDH. In order to further characterize the role of RIPK1 in DG, we performed a GeneOntology and Pathway Enrichment Analysis using the Xena platform’s differential expressiontool. 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 molecularprocesses crucial for cancer progression were studied: proliferation, epithelial-mesenchymaltransition, immune cell infiltration and cell death pathways. Briefly, the results showedsignificant differences in genes related to increased cellular dedifferentiation,proinflammatory cell death pathways and tumor infiltrating immune cells gene signatures(Welch's t-test).ConclusionsRIPK1 over-expression is associated with a poor prognosis in DG. This fact, together withour in silico results suggest that RIPK1 may play a crucial role for glioma progression,positioning it as a promising candidate for therapeutic targeting.