Comprehensive analysis reveals PLK3 as a promising immune target and prognostic indicator in glioma.

Abstract

Background: PLK3, which played an important role in cell cycle progression and stress response, was identified as highly expressed in various carcinomas. However, the functions, molecular characteristics, and prognostic value of PLK3 in glioma remained unexplored.

Methods: We analyzed PLK3 expression in glioma samples from multiple databases. Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma, and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression. Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration. The trans-well assay for PLK3 on the immune cells recruitment was also determined. Additionally, we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.

Results: We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma, and further validated that PLK3 promoted glioma progression. PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression. Specifically, we revealed that CD8⁺ and CD4⁺ Tcell infiltration was decreased in Plk3 overexpressed xenografts. Furthermore, it was predicted that PLK3 was synergistic with other checkpoint members in glioma. In general, high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.

Conclusion: Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas, and we validated that PLK3 could promote the GBM progress in vitro and in vivo. Furthermore, PLK3 played important roles in Tcell and neutrophil immune response in glioma. Besides, the conspicuous association between PLK3 and other immune checkpoints was also observed. Crucially, high-level PLK3 expression was revealed to be related to poor clinical prognosis. These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.