Abstract P110: DPYD Overexpression Promotes Malignant Phenotypes in Glioblastoma Through Enhanced Proliferation and Migration
Yuganthini Vijayanathan, Matriano Isaiah Riley Del Rosario, Akmal Reyza Mohamad Rashid, Kim Tat Yeoh, Ivy, AW HoAbstract
Introduction:
Glioblastoma (GBM) is a highly aggressive brain tumor driven by metabolic reprogramming. Dihydropyrimidine Dehydrogenase (DPYD), a key enzyme in pyrimidine catabolism, is linked to cancer metabolism, but its role in GBM is unclear. This study examined the clinical relevance of DPYD and its role in driving proliferation and migration in human glioma cells.
Methods:
Analysis of TCGA and IvyGAP datasets identified metabolism-related genes differentially expressed in the tumor core region versus the leading edge and infiltrating tumor regions (tumor periphery). DPYD, upregulated in tumor core, was shortlisted and assessed for subtype specificity and prognosis using GlioVis. Endogenous DPYD expression in U251MG human glioma cells and immortalized normal human astrocytes (iNHA) was quantified by qPCR. For functional studies, U251MG were stably transduced with a FLAG-tagged lentiviral DPYD construct (U251-DPYD), and vector control (U251-vector) were generated and validated via western blotting. Proliferation was measured via Click-iT™ EdU incorporation assay (S-phase), Ki-67 immunofluorescence (G1–M), and Cyclin A protein levels (S/G2) by western blotting. Migration was evaluated using a transwell assay.
Results:
Clinical datasets analyses identified DPYD as a candidate gene, showing 2.6-fold upregulation in the GBM tumor core versus tumor periphery, elevated expression in the mesenchymal (when compared to classical and proneural subtypes), and significant association with poor prognosis. In vitro, U251MG cells exhibited 4.0-fold increase in endogenous DPYD expression compared to iNHA. Transduced U251-DPYD cells showed increased DPYD expression (1.6-fold), and detection of FLAG-tagged protein confirmed successful transduction relative to U251-vector. Functionally, U251-DPYD cells showed 4.0-fold increase in EdU incorporation, with modest but consistent increases in Ki-67 (1.5-fold) and Cyclin A (1.2-fold), supporting enhanced proliferative activity. Additionally, U251-DPYD cells exhibited a 30% increase in migratory capacity compared to U251-vector.
Conclusion:
Together, these findings identify DPYD as a potential contributor to GBM malignancy and warrant further investigation into its role in disease progression
Citation Format:
Yuganthini Vijayanathan, Matriano Isaiah Riley Del Rosario, Akmal Reyza Mohamad Rashid, Kim Tat Yeoh, Ivy, AW Ho. DPYD Overexpression Promotes Malignant Phenotypes in Glioblastoma Through Enhanced Proliferation and Migration [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P110.