The oncogenic role of CCDC34 in lower-grade gliomas: prognostic significance and therapeutic potential.

PURPOSE: To investigate the prognostic significance, molecular mechanisms, and therapeutic potential of CCDC34 in lower-grade gliomas (LGG). METHODS: Data from TCGA, CGGA, and GEO databases, comprising 1,064 LGG patient samples, were analyzed to evaluate the correlation between CCDC34 expression and clinical outcomes. Kaplan-Meier analysis, Cox regression, PPI, Virtual screening and meta-analysis were conducted to assess its prognostic significance. Mechanistic studies included DNA methylation analysis and KEGG pathway enrichment to explore regulatory mechanisms. In vitro and in vivo experiments were performed to validate its effects on tumor cell proliferation, migration, and tumorigenesis. RESULTS: Elevated CCDC34 expression was significantly associated with advanced tumor grade, recurrence, and poor overall survival. Meta-analysis confirmed CCDC34 as an independent risk factor for prognosis. DNA methylation analysis revealed that CCDC34 expression is negatively regulated by cg19157696 methylation, with hypermethylation correlating with better patient outcomes. Pathway enrichment analyses showed that CCDC34 is involved in critical oncogenic pathways, including PI3K-Akt, HIF-1, and Notch, which promote tumor cell proliferation, invasion, and immune microenvironment modulation. It has also been found that five types of small-molecule drugs may have the potential to inhibit the expression of CCDC34. Functional validation demonstrated that silencing CCDC34 significantly reduced LGG cell proliferation, migration, and tumor formation in vitro and in vivo. CONCLUSIONS: CCDC34 acts as an oncogene in LGG and is strongly associated with poor prognosis and malignant progression. Its regulation via DNA methylation and involvement in key pathways highlight its potential as a prognostic biomarker and therapeutic target.