Identification and validation of neurotrophic factor-related gene signatures in glioblastoma and Parkinson's disease

作者全名："Zhao, Songyun; Chi, Hao; Yang, Qian; Chen, Shi; Wu, Chenxi; Lai, Guichuan; Xu, Ke; Su, Ke; Luo, Honghao; Peng, Gaoge; Xia, Zhijia; Cheng, Chao; Lu, Peihua"

作者地址："[Zhao, Songyun; Cheng, Chao] Nanjing Med Univ, Dept Neurosurg, Wuxi Peoples Hosp, Wuxi, Jiangsu, Peoples R China; [Chi, Hao; Su, Ke; Peng, Gaoge] Southwest Med Univ, Clin Med Coll, Luzhou, Peoples R China; [Yang, Qian; Chen, Shi] Chongqing Med Univ, Clin Mol Med Testing Ctr, Affiliated Hosp 1, Chongqing, Peoples R China; [Wu, Chenxi; Lu, Peihua] Nanjing Med Univ, Dept Oncol, Wuxi Peoples Hosp, Wuxi, Jiangsu, Peoples R China; [Lai, Guichuan] Chongqing Med Univ, Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Chongqing, Peoples R China; [Xu, Ke] Chongqing Gen Hosp, Dept Oncol, Chongqing, Peoples R China; [Luo, Honghao] Xichong Peoples Hosp, Dept Radiol, Nanchong, Peoples R China; [Xia, Zhijia] Ludwig Maximilians Univ Munchen, Dept Gen Visceral & Transplant Surg, Munich, Germany; [Lu, Peihua] Nanjing Med Univ, Dept Clin Res Ctr, Wuxi Peoples Hosp, Wuxi, Jiangsu, Peoples R China"

通信作者："Cheng, C (通讯作者)，Nanjing Med Univ, Dept Neurosurg, Wuxi Peoples Hosp, Wuxi, Jiangsu, Peoples R China.; Lu, PH (通讯作者)，Nanjing Med Univ, Dept Oncol, Wuxi Peoples Hosp, Wuxi, Jiangsu, Peoples R China.; Xia, ZJ (通讯作者)，Ludwig Maximilians Univ Munchen, Dept Gen Visceral & Transplant Surg, Munich, Germany.; Lu, PH (通讯作者)，Nanjing Med Univ, Dept Clin Res Ctr, Wuxi Peoples Hosp, Wuxi, Jiangsu, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000934467300001

JCR分区：Q1

影响因子：7.3

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：PD; GBM; NFRG; immune cell infiltration; machine learning

摘要："BackgroundGlioblastoma multiforme (GBM) is the most common cancer of the central nervous system, while Parkinson's disease (PD) is a degenerative neurological condition frequently affecting the elderly. Neurotrophic factors are key factors associated with the progression of degenerative neuropathies and gliomas. MethodsThe 2601 neurotrophic factor-related genes (NFRGs) available in the Genecards portal were analyzed and 12 NFRGs with potential roles in the pathogenesis of Parkinson's disease and the prognosis of GBM were identified. LASSO regression and random forest algorithms were then used to screen the key NFRGs. The correlation of the key NFRGs with immune pathways was verified using GSEA (Gene Set Enrichment Analysis). A prognostic risk scoring system was constructed using LASSO (Least absolute shrinkage and selection operator) and multivariate Cox risk regression based on the expression of the 12 NFRGs in the GBM cohort from The Cancer Genome Atlas (TCGA) database. We also investigated differences in clinical characteristics, mutational landscape, immune cell infiltration, and predicted efficacy of immunotherapy between risk groups. Finally, the accuracy of the model genes was validated using multi-omics mutation analysis, single-cell sequencing, QT-PCR, and HPA. ResultsWe found that 4 NFRGs were more reliable for the diagnosis of Parkinson's disease through the use of machine learning techniques. These results were validated using two external cohorts. We also identified 7 NFRGs that were highly associated with the prognosis and diagnosis of GBM. Patients in the low-risk group had a greater overall survival (OS) than those in the high-risk group. The nomogram generated based on clinical characteristics and risk scores showed strong prognostic prediction ability. The NFRG signature was an independent prognostic predictor for GBM. The low-risk group was more likely to benefit from immunotherapy based on the degree of immune cell infiltration, expression of immune checkpoints (ICs), and predicted response to immunotherapy. In the end, 2 NFRGs (EN1 and LOXL1) were identified as crucial for the development of Parkinson's disease and the outcome of GBM. ConclusionsOur study revealed that 4 NFRGs are involved in the progression of PD. The 7-NFRGs risk score model can predict the prognosis of GBM patients and help clinicians to classify the GBM patients into high and low risk groups. EN1, and LOXL1 can be used as therapeutic targets for personalized immunotherapy for patients with PD and GBM."

基金机构："General project of Wuxi commission of Health [MS201933, T202120]"

基金资助正文："Funding This work was supported by General project of Wuxi commission of Health (MS201933, T202120)."