Abstract 3334: Expression analyses of SLC3A2 and its associated genes in glioma progression

Abstract High grade gliomas (grade III and IV) including glioblastomas (GBM, grade IV, IDH wild type), are highly aggressive brain tumors with limited treatment options and poor prognosis. Tumor recurrence is inevitable with standard methods including surgical debulking, radio- and chemotherapies. For this reason, a broad range of studies focus on the discovery of diagnostic and therapeutic markers to cure the malign disease. SLC3A2, a polyamine transporter, has been implicated in chemoresistance of tumors and identified as a prognostic marker in renal cell carcinoma. Accordingly, in this study, we examined i) the prognostic impact of SLC3A2 expression in gliomas, ii) its association with differentially expressed gene networks, and iii) its molecular characteristics to elucidate its role in glioma biology. Immunohistochemical and western blot analyses revealed significant overexpression of SLC3A2 in high grade glioma tissues compared to controls. Robust SLC3A2 expression was also observed in a pannel of GBM cell lines. Cohort analysis of the TCGA French glioma patient dataset (n=264) stratified patients by SLC3A2 expression, showing a significant survival advantage for low expressors across glioma grades (p=.0021). This survival benefit was particularly pronounced in high-grade gliomas, underscoring the link between SLC3A2 expression and tumor aggressiveness. Differentially expressed gene analysis identified several druggable genes co-regulated with SLC3A2. Differential expression of VEGFA and ADM in SLC3A2 high-expressors suggests a potential role of Slc3a2 in tumor angiogenesis, while links to CHI3L1 and CXCL14 imply roles in enhancing tumor invasiveness and immune modulation. In contrast, TOX3 and SNAP91 were enriched in SLC3A2 low-expressors, pointing to suppression of neuronal differentiation and maintenance of glioma stem-like properties. Weighted gene co-expression analysis linked SLC3A2 to genes involved in cytoskeletal remodeling (DMPK), and chromatin regulation (RNF40), reinforcing its role in tumor plasticity. Negative correlations with SIRT1 and KAT6B suggest a metabolic shift favoring tumor-specific survival and growth. These findings lay the groundwork for exploring SLC3A2 as a therapeutic target and its potential in personalized therapies. Further studies will clarify its mechanistic role in gliomagenesis and its utility in clinical applications. This study was supported by The Scientific Research Commision of İstanbul Medipol University with project number 2023-66. Citation Format: Birnur Sinem Karaoglan, Ozan Topcu, Ecren Ecem Uzlu, Osman Aliskan, Thomas Mohr, Nazli Cakici, Ahmet Tulgar Basak, Asli Cakir, Nihal Karakas. Expression analyses of SLC3A2 and its associated genes in glioma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3334.