Identification and validation of a novel Parkinson-Glioma feature gene signature in glioma and Parkinson's disease Provisionally Accepted

Hengrui Zhang¹ Jiwei Wang¹ Nan Su¹ Ning Yang¹ Xinyu Wang¹ Chao Li^1*

• ¹Qilu Hospital, Shandong University, China

The prognosis for glioma is generally poor, and the 5-year survival rate for patients with this disease has not shown significant improvement over the past few decades. PD is a prevalent movement disorder, ranking as the second most common neurodegenerative disease after Alzheimer's disease. Although Parkinson's disease and glioma are distinct diseases, they may share certain underlying biological pathways that contribute to their development.Objective: This study aims to investigate the involvement of genes associated with Parkinson's disease in the development and prognosis of glioma.We obtained datasets from the TCGA, CGGA, and GEO databases. Eight machine learning algorithms were used to identify PGFGs. PGFGs associated with glioma prognosis were identified through univariate Cox analysis. A risk signature was constructed based on PGFGs using Cox regression analysis and LASSO. We Subsequently validated its predictive ability using various methods, including ROC curves, calibration curves, KM survival analysis, C-index, DCA, independent prognostic analysis, and stratified analysis. To validate the reproducibility of the results, similar work was performed on three external test datasets. Additionally, a meta-analysis was employed to observe the heterogeneity and consistency of the signature across different datasets. We also compared the differences in genomic variations, functional enrichment, immune infiltration, and drug sensitivity analysis based on risk scores. We identified 30 PGFGs, of which 25 were found to be significantly associated with glioma survival. The prognostic signature, consisting of 19 genes, demonstrated excellent predictive performance for 1-, 2-, and 3-year OS of glioma. The signature emerged as an independent prognostic factor for glioma OS, surpassing the predictive performance of traditional clinical variables. Notably, we observed differences in the TME, levels of immune cell infiltration, immune gene expression, and drug resistance analysis among distinct risk groups. These findings may have significant implications for the clinical treatment of glioma patients.The expression of genes related to Parkinson's disease is closely associated with the immune status and prognosis of glioma patients, potentially regulating glioma pathogenesis through multiple mechanisms. The interaction between genes associated with PD and the immune system during glioma development provides novel insights into the molecular mechanisms and targeted therapies for glioma.