Functional clustering analysis identifies specific subtypes of aldehyde dehydrogenase associated with glioma immunity

BACKGROUND: As a novel cancer stem cell marker, the biological functions of aldehyde dehydrogenases (ALDH enzymes) are a hot topic in current cancer research. However, there is a lack of systematic understanding of ALDH enzymes, which has hindered the translation of targeted therapies from bench work into the clinic. METHODS: Based on transcriptome data from 999 glioma patients, functional clustering analysis was performed to reveal the functional phenotypes of ALDH isoforms. Subsequently, ALDH subgroups closely related to gliomas were identified by Cox survival analysis. Finally, gene set variation analysis (GSVA) and Pearson correlation analysis were used to explore the biological functions of ALDH enzymes. RESULTS: Our study found that ALDH enzymes could be classified into 5 subgroups, among which 3 groups were closely related to malignant progression and the prognosis of gliomas. We found that ALDH enzymes were closely related to gene mutations, which were most likely caused by changes in DNA repair functions. Further studies revealed that ALDH enzymes affect tumor immune functions, especially the expression of immune checkpoints. The effectiveness of immune checkpoint inhibitors in treating glioma might be improved by altering the expression of ALDH enzymes in specific subgroups. CONCLUSIONS: This study comprehensively revealed the biological functions of ALDH enzymes in glioma and provided details about the potential clinical application of targeted therapy for ALDH enzymes.