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Updated: Jul 17, 2025
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Higher Mixed lineage Kinase Domain-like protein (MLKL) is associated with worst overall survival in adult-type
Guilherme Afonso Vergara1, Gisele Cristine Eugenio1, Suzana Maria Fleury Malheiros2
1Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
Introduction:
Recently, the search for novel molecular markers in adult-type diffuse gliomas has grown substantially, yet with few novel breakthroughs. As the presence of a necrotic center is a differential diagnosis for more aggressive entities, we hypothesized that genes involved in necroptosis may play a role in tumor progression.
Aim:
Given that MLKL is the executioner of the necroptotic pathway, we evaluated whether this gene would help to predict prognosis of adult gliomas patients.
Methods:
We analyzed a publicly available retrospective cohort (n = 530) with Kaplan Meier survival analysis (p<0.0001) and both uni- and multivariate Cox regression models.
Results:
We determined that MLKL is an independent predictive prognostic marker for overall survival in these patients (HR: 2.56, p<0.001), even when controlled by the CNS5 gold-standard markers, namely IDH mutation and 1p/19q Codeletion (HR: 1.68, p = 0.013). These findings were confirmed in a validation cohort (n = 325), using the same cutoff value. Interestingly, higher expression of MLKL is associated with worse clinical outcome for adult-type diffuse glioma patients, which is opposite to what was found in other cell cancer types, suggesting that necroptosis undertakes an atypical detrimental role in glioma progression.
