Integrative analysis of polo-like kinase family identifies a prognostic signature and validates PLK2 as a therapeutic target in glioma.

BACKGROUND: Glioma is a common malignant tumor of the central nervous system, characterized by aggressive behavior and poor prognosis. The polo-like kinase (PLK) gene family plays a crucial role in cell cycle regulation, but its expression and functional roles in glioma remain incompletely understood. This study aimed to systematically characterize the expression landscape and prognostic significance of the PLK gene family in glioma and to experimentally evaluate the therapeutic potential of PLK2 inhibition. METHODS: We performed a comprehensive analysis using RNA transcriptome sequencing data and clinical information from 1,018 glioma patients. The expression patterns and prognostic significance of PLK family genes were evaluated in relation to tumor grade and molecular markers. A prognostic model based on PLK gene expression was developed and validated. Gene Ontology (GO) enrichment analysis was conducted to explore PLK2-associated biological functions. Functional experiments, including Cell Counting Kit-8 (CCK-8) viability assay, colony formation assay, and transwell migration assay, were performed to assess the effect of the PLK2-specific inhibitor ON1231320 on glioblastoma (GBM) cell lines. RESULTS: PLK1-4 were highly expressed in high-grade gliomas and associated with poor prognosis, whereas PLK5 expression correlated with better outcomes. The PLK-based prognostic model demonstrated strong predictive performance for 1-, 3-, and 5-year survival [area under the curve (AUC) =0.73, 0.80, and 0.80, respectively]. GO enrichment analysis suggested that high PLK2 expression is involved in extracellular matrix-related pathways, while low expression may be linked to neural development. Functional assays confirmed that ON1231320 significantly inhibited GBM cell proliferation and migration. CONCLUSIONS: Our study highlights the prognostic value of the PLK gene family in glioma and identifies PLK2 as a promising therapeutic target. The PLK2 inhibitor ON1231320 shows potential as an anti-GBM agent and warrants further investigation in preclinical and clinical studies.