Abstract Details

Title Role of LRRK2 in Glioblastoma: Oncogene or Tumor Suppressor?

Topic Neuro-oncology

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 6-009

Objective To investigate the role of leucine-rich repeat kinase 2 (LRRK2) in glioblastoma (GBM) biology.

Background GBM is an aggressive brain tumor with limited treatment options. While LRRK2 gain-of-function variants are linked to autosomal-dominant Parkinson’s disease, emerging evidence suggests a potential tumor-suppressive role in GBM. Prior studies suggest that elevated LRRK2 expression may be associated with improved outcomes in GBM, particularly in TP53 wild-type tumors.

Design/Methods

In silico analyses were performed using GlioVis, the Chinese Glioma Genome Atlas (CGGA), cBioPortal, and the Human Protein Atlas (HPA). LRRK2 mRNA and protein expression were examined in relation to overall survival (OS) and key GBM prognostic markers (MGMT, TP53, ATRX, CDKN2A/B). Subgroup analyses were performed across transcriptional subtypes (classical, mesenchymal, proneural).

Results

LRRK2 mRNA expression trended lower in GBM versus non-tumor tissue (GlioVis: p = 0.40). Higher LRRK2 mRNA levels correlated with non-significant OS improvement in primary GBM (GlioVis: HR = 1.19, p = 0.33; CGGA: p = 0.08; cBioPortal: HR = 0.93, p = 0.83), but with significantly improved OS in recurrent GBM (CGGA: p = 0.047). Elevated LRRK2 protein expression was associated with improved OS (HPA: p = 0.034). LRRK2 mRNA expression negatively correlated with TP53 (GlioVis: r = -0.30, p<0.001), CDKN2A (CGGA: r = -0.272, p<0.001), and CDKN2B (CGGA: r = -0.15, p = 0.05), while positively correlated with IDH1 (CGGA: r = 0.291, p<0.001) and ATRX (CGGA: r = 0.231, p = 0.03). Subtype analyses showed persistent negative correlations with TP53, CDKN2A/B, and MGMT in classical and mesenchymal GBM.

Conclusions

Elevated LRRK2 expression, particularly in recurrent GBM, is associated with improved OS, supporting LRRK2’s potential tumor-suppressive role. The variable correlations across GBM transcriptional subtypes suggest complex, subtype-dependent function for LRRK2, warranting further investigation.

Authors/Disclosures
Michele Persico, MD PRESENTER	Dr. Persico has nothing to disclose.
Jorge L. Jimenez Macias, PhD	Dr. Jimenez Macias has nothing to disclose.
Abdulkadir Mohamed, MD	Dr. Mohamed has nothing to disclose.
Saud Alhusaini, MD, PhD (Brown University)	Dr. Alhusaini has nothing to disclose.
Renee Read, PhD	The institution of Dr. Read has received research support from Bausch Health.

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