Abstract 2727: Overexpression of protocadherin related 15 (PCDH15) gene predicts better prognosis in low-grade glioma patients

Abstract

Background: Gliomas are the most common tumors arising from the brain. According to the WHO classification, gliomas are divided into low- and high-grade gliomas based on their aggressiveness and degrees of differentiation. Protocadherin Related 15 (PCDH15) gene is a member of the cadherin superfamily that encode membrane proteins involved in cell-cell adhesion. In this study, we aimed to investigate the prognostic value of PCDH15 expression in Low-Grade Gliomas (LGG) and Glioblastoma Multiforme (GBM). Methods: We conducted a bioinformatics analysis for PCDH15 in LGG and GBM patients’ data using their respective datasets from the Cancer Genomic Atlas (TCGA). GEPIA and GENT2 web-based tools were used to confirm the differential expression of PCDH15 in LGG and GBM patients in comparison with normal brain tissue. We used the cBioPortal database to compare PCDH15 expression across molecular and histological glioma subtypes. Also, the SurvExpress tool was used to assess the prognostic value of PCDH15 on overall survival (OS). To further understand the underlying molecular biology of PCDH15’s function, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for significantly co-expressed genes (|spearman correlation coefficient|≥ 0.5) with PCDH15 using the DAVID 6.8 bioinformatics tool. Results: LGG and GBM both had statistically significant differences in PCDH15 expression compared with normal brain tissue. PCDH15 expression was significantly higher in LGG patients compared with GBM patients (mean log2 (TPM + 1): 9.5 vs 5.6, P < 0.0001), with the highest expression in patients with mutated IDH genes. In the LGG cohort, higher PCDH15 expression was associated with longer OS (hazard ratio: 2.44, 95% confidence interval: 1.69 - 3.53, P = 1.949E-6) while no significant difference was found in the GBM cohort (hazard ratio: 1.07, 95% confidence interval: 0.74 - 1.53, P = 0.7304). GO analyses for co-expressed genes in LGG indicated a role in the biological process (BP) DNA-templated regulation of transcription with a cellular component (CC) in the nucleus and the molecular functions (MF) “histone demethylase activity”, “hydrolase activity, acting on acid anhydrides” and “zinc ion binding”. While in GBM, GO analysis showed enrichment in the BP terms, “neuron cell-cell adhesion”, “positive regulation of synapse assembly”, and the CC terms, “cell junction”, “axon”, “plasma membrane”. KEGG pathway analysis did not retrieve any significantly enriched pathways in both diseases. Conclusion: Our findings demonstrate a unique pattern of PCDH15 overexpression in low-grade gliomas which was translated into a substantial impact on patients’ survival. Functional enrichment analysis indicated transcription regulation as a potential mechanism for PCDH15 in LGG, further supporting PCDH15's potential as a therapeutic target. Citation Format: Hassan Mohammed Abushukair, Bayan Osama Abu Alragheb. Overexpression of protocadherin related 15 (PCDH15) gene predicts better prognosis in low-grade glioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2727.