Abstract
Objective
This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM.
Methods
Utilizing the GEPIA2 and TCGA databases, we contrasted the expression levels of PLP2 in GBM against normal tissue. We utilized GEPIA2 and LinkedOmics for survival analysis, recognized genes co-expressed with PLP2 via cBioPortal and GEPIA2, and implemented GO and KEGG analyses. The STRING database facilitated the construction of protein-protein interaction networks. We evaluated the relationship of PLP2 with tumor immune infiltrates using ssGSEA and the TIMER 2.0 database. An IHC assay assessed PLP2 and PDL-1 expression in GBM tissue, and the Drugbank database aided in identifying potential PLP2-targeting compounds. Molecular docking was accomplished using Autodock Vina 1.2.2.
Results
PLP2 expression was markedly higher in GBM tissues in comparison to normal tissues. High PLP2 expression correlated with a decrease in overall survival across two databases. Functional analyses highlighted a focus of PLP2 functions within leukocyte. Discrepancies in PLP2 expression were evident in immune infiltration, impacting CD4+ T cells, neutrophils, myeloid dendritic cells, and macrophages. There was a concomitant increase in PLP2 and PD-L1 expression in GBM tissues, revealing a link between the two. Molecular docking with ethosuximide and praziquantel yielded scores of −7.441 and −4.295 kcal/mol, correspondingly.
Conclusion
PLP2’s upregulation in GBM may adversely influence the lifespan of GBM patients. The involvement of PLP2 in pathways linked to leukocyte function is suggested. The positive correlation between PLP2 and PD-L1 could provide insights into PLP2’s role in glioma modulation. Our research hints at PLP2’s potential as a therapeutic target for GBM, with ethosuximide and praziquantel emerging as potential treatment candidates, especially emphasizing the potential of these compounds in GBM treatment targeting PLP2.
Plain Language Summary
Glioblastoma is the most prevalent and aggressive malignant glioma. PLP2, a protein found to be upregulated in several cancers and neurological diseases, has drawn attention for its potential role in glioblastoma treatment. With advances in immunotherapy and improved understanding of tumor-immune system interactions, PD-1/PD-L1 inhibitors are gaining increasing interest for treating glioblastomas.
In glioblastoma patients, overexpression of PLP2 may worsen overall survival rates. PLP2 is believed to be involved in key pathways related to leukocyte, and a connection was found between PLP2 and PD-L1, suggesting that PLP2 might influence glioblastomas through this interaction. The potential use of PD-1/PD-L1 inhibitors in treating glioblastomas has emerged as a result of these findings.
Moreover, the study highlights the potential of drugs such as ethosuximide and praziquantel to target PLP2 in glioblastoma therapy. This research emphasizes the promising role of PLP2 as a therapeutic target for glioblastoma, where praziquantel and ethosuximide could be employed. Overall, the study presents a new therapeutic target for glioblastoma and demonstrates the potential of PD-1/PD-L1 inhibitors, praziquantel, and ethosuximide in this treatment approach.
Ethical Statement
Patients were consented by an informed consent process and certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki. This study has been approved by Qingdao University Affiliated Hospital Ethics Committee.
Acknowledgments
I would like to thank all teachers who have helped in my research.
Disclosure
The authors report no conflicts of interest in this work.