Single-cell sequencing uncovers the mechanistic role of DAPK1 in glioma and its diagnostic and prognostic implications

• Published in: Frontiers in immunology Vol. 15; p. 1463747
• Main Authors: Yu, Tian-Hang, Ding, Yan-Yu, Zhao, Si-Guo, Zhao, Jie-Hui, Gu, Yu, Chen, Dong-Hui, Zhang, Fang, Hong, Wen-Ming
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2024
• Subjects: Biomarkers, Tumor - genetics; Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Brain Neoplasms - mortality; DAPK1; Death-Associated Protein Kinases - genetics; Death-Associated Protein Kinases - metabolism; diagnosis; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; glioma; Glioma - diagnosis; Glioma - genetics; Glioma - mortality; Humans; immune infiltration; Prognosis; Single-Cell Analysis - methods; tumor immune microenvironment; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; diagnosis; glioma; immune infiltration; DAPK1; tumor immune microenvironment; prognosis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1463747

We conducted an investigation into the characteristics of single-cell differentiation data in gliomas, with a focus on developing DAPK1-based prognostic markers to predict patient outcomes. Dysregulated expression of DAPK1 has been associated with the invasive behavior of various malignancies, including gliomas. However, the precise role and underlying mechanisms of DAPK1 in gliomas remain inadequately understood. We performed analyses on RNA-seq and microarray datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), in addition to single-cell RNA sequencing (scRNA-seq) data from glioma patients available in GEO. Utilizing the Seurat R package, we identified gene clusters associated with survival from the scRNA-seq data. Prognostic models were developed using LASSO and stepwise regression algorithms. Furthermore, we assessed the predictive potential of these genes within the immune microenvironment and their relevance in immunotherapy contexts. Our scRNA-seq data analysis revealed 32 distinct cell clusters corresponding to 10 cell types. Through dimensionality reduction and clustering, we identified three glial cell subpopulations based on their differentiation trajectories. DAPK1, serving as a marker gene for the terminal subpopulation, exhibited an association with poor prognosis. DAPK1-based prognostic models show promise for accurately predicting outcomes in glioblastoma and glioma. An in-depth examination of DAPK1's specific mechanisms in glioblastoma could elucidate its role in immunotherapy response. Targeting the DAPK1 gene may offer therapeutic benefits for glioma patients.