Abstract
Gliomas are malignant tumors that originate from the central nervous system. The aldehyde dehydrogenase family has been documented to affect cancer progression; however, its role in gliomas remains largely unexplored. Bulk RNA-seq analysis and single-cell RNA-Seq analysis were performed to explore the role of the aldehyde dehydrogenases family in gliomas. Training cohort contained The Cancer Genome Atlas data, while data from Chinese Glioma Genome Atlas and Gene Expression Omnibus were set as validation cohorts. Our scoring system based on the aldehyde dehydrogenases family suggested that high-scoring samples were associated with worse survival outcomes. The enrichment score of pathways were calculated by AUCell to substantiate the biofunction prediction results that the aldehyde dehydrogenases family affected glioma progression by modulating tumor cell proliferation, migration, and immune landscape. Tumor immune landscape was mapped from high-scoring samples. Moreover, ALDH3B1 and ALDH16A1, two main contributors of the scoring system, could affect glioblastoma cell proliferation and migration by inducing cell-cycle arrest and the epithelial-mesenchymal transition. Taken together, the aldehyde dehydrogenases family could play a significant role in the tumor immune landscape and could be used to predict patient prognosis. ALDH3B1 and ALDH16A1 could influence tumor cell proliferation and migration.
Highlights
Gliomas are the most common cancer type of the central nervous system, representing approximately 80% of malignant brain tumors
Analysis of the The Cancer Genome Atlas (TCGA) dataset showed higher expression levels of ALDH16A1, ALDH3B1, ALDH7A1, ALDH1A2, ALDH3A1 and ALDH1A3 in GBM compared to LGG, while ALDH4A1, ALDH8A1, ALDH1A1, ALDH6A1, ALDH2, ALDH5A1, ALDH1L2 expressions were lower in GBM (Figure 1A)
Lower expressions of ALDH1A1, ALDH6A1, ALDH2, ALDH5A1 were observed in GBM compared to LGG, while ALDH16A1, ALDH3B1 and ALDH3A1 were preferentially enriched in GBM (Figures 1B–D)
Summary
Gliomas are the most common cancer type of the central nervous system, representing approximately 80% of malignant brain tumors. Glioblastoma (GBM) is the most aggressive type of gliomas [1, 2], with a reported overall survival time of only 15-18 months [3, 4]. The identification of molecular signatures has provided new insights into glioma prognosis prediction [6]. Isocitrate dehydrogenase (IDH) 1/2 mutations and 1p19q co-deletion have been considered glioma prognosis-related biomarkers [7]. Classification based on these signatures can be used to subdivide GBM into three subtypes (classical, proneural and mesenchymal) and assist during clinical practice for treatment selection and prognosis prediction [8]. Since gliomas are highly heterogeneous tumors, it is vital to identify novel biomarkers to help clinicians during the differential diagnosis and make treatment decisions
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