PSMC4 promotes low-grade glioma progression and predicts poor prognosis – Research

Background:

Low-grade gliomas (LGG) are aggressive brain tumors with high rates of recurrence and poor prognosis. PSMC4, a proteasome subunit, plays a role in various cancers, but its function in LGG remains poorly understood. This study explores PSMC4’s impact on LGG progression.

Methods:

PSMC4 expression in LGG patients was analyzed using data from TCGA, CGGA, and GEO. Kaplan-Meier and Cox regression models assessed survival outcomes. Gene Set Enrichment Analysis (GSEA) identified key pathways affected by PSMC4. Immune infiltration was evaluated using the TIMER database. In vitro, SHG44 cells were transfected with shRNA targeting PSMC4, and assays for cell proliferation, migration, clonogenicity, and invasion were performed. In vivo xenograft assays were also conducted.

Results:

High PSMC4 expression was linked to higher tumor grade and poor prognosis in LGG patients. Kaplan-Meier analysis revealed shorter overall survival for patients with high PSMC4 expression. ROC curve analysis confirmed the diagnostic value of PSMC4 for predicting poor prognosis. GSEA identified pathways like Notch, Toll-like receptor, and VEGF signaling that may be regulated by PSMC4. In vitro, PSMC4 knockdown significantly reduced SHG44 and T98 cell proliferation, migration, and invasion, while clonogenic assays showed decreased colony formation. In vivo, PSMC4 knockdown led to smaller tumor volumes in xenograft models, confirming its role in tumor progression.

Conclusion:

PSMC4 overexpression promotes LGG progression and may be an independent marker of poor prognosis. Targeting PSMC4 can reduce tumor growth and metastasis, providing a promising strategy for LGG treatment. Further research on its regulatory mechanisms and clinical implications is warranted.