Abstract
Precision therapy for glioma remains a major challenge due to tumor heterogeneity. The Origin Recognition Complex Subunit 6 (ORC6) is a crucial regulator of DNA replication initiation. This study aims to investigate the expression of ORC6 in gliomas and its relationship with survival rates and malignancy, while screening potential drugs targeting its functional network. By integrating multiple bioinformatics approaches with structure-based virtual screening, retrospective RNA sequencing data analysis was performed using patients from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. A protein-protein interaction (PPI) network was constructed from ORC6-coexpressed genes to identify core hubs. Molecular docking was employed to screen a library of natural compounds and known drugs against these hub targets. Research has revealed that ORC6 is significantly upregulated in high-grade gliomas, with its elevated expression associated with poor survival outcomes and immune inflammatory responses. Network analysis identified five core hub genes (ORC1, ORC2, MCM2, MCM6, CDC45) central to DNA replication. Molecular docking revealed that several compounds, including the natural flavonoid Baicalein and the FDA-approved drug Palbociclib, exhibited high binding affinity to these hub targets. ORC6 represents a highly promising novel target for precision therapy in glioma. Potential approaches to target this pathway include disrupting the ORC6-replication axis using existing drugs (such as palbociclib) or natural products (such as baicalin).