C-Terminal Domain Nuclear Envelope Phosphatase 1 (CTDNEP1) is Associated with a Neuronal-Like Proliferative Transcriptional Program in Glioblastoma
Yu-Kai Sung, Wen-Shin Song, Pei-Chi ChangBackground:
Glioblastoma multiforme (GBM) is the most lethal subtype of glioma. Therapeutic resistance frequently leads to tumor recurrence and poor patient prognosis. CTD nuclear envelope phosphatase 1 (CTDNEP1) is a nuclear envelope-associated phosphatase involved in membrane biogenesis and cellular signaling, but its role in glioma is unknown.
Aim:
This study aimed to investigate the functional role of CTDNEP1 in GBM.
Methods:
Transcriptome and clinical data were obtained from The Cancer Genome Atlas dataset. Differential expression analysis, tumor grade correlation, Kaplan–Meier survival analysis, and Cox regression analysis were performed to evaluate the clinical role of CTDNEP1. Gene correlation, gene set enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Gene Ontology enrichment analysis were conducted to explore CTDNEP1-associated pathways. Single-cell RNA sequencing datasets were analyzed to determine the cellular distribution of CTDNEP1. Finally, CIBERSORT analysis was performed to evaluate its association with immune cell infiltration and the tumor microenvironment.
Results:
CTDNEP1 expression was highly elevated in glioma tissues and positively correlated with tumor grade. High CTDNEP1 expression was associated with poor overall survival and served as an independent prognostic factor. Functional enrichment analyses revealed that CTDNEP1-associated genes were enriched in neuronal signaling pathways, ion channel activity, and cell cycle-related processes. Single-cell analysis showed that CTDNEP1 is mainly expressed in tumors and myeloid cells. CIBERSORT analysis showed that high levels of CTDNEP1 were associated with several immune cell types.
Conclusion:
CTDNEP1 is a novel prognostic biomarker associated with glioma progression, suggesting its potential as a therapeutic target.