Integrating RNA-seq and scRNA-seq to explore the biological significance of NAD + metabolism-related genes in the initial diagnosis and relapse of childhood B-cell acute lymphoblastic leukemia

作者：Chao Lin, Jiaqi Xu, Guichao Zhong, Hui Chen, Hongman Xue, Mo Yang, Chun Chen · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.1043111 · 被引用次数：15 · 研究领域：Acute Lymphoblastic Leukemia research、Acute Myeloid Leukemia Research、Lung Cancer Research Studies

Background: Nicotinamide Adenine Dinucleotide (NAD) depletion is reported to be a potential treatment for B-cell Acute Lymphoblastic Leukemia (B-ALL), but the mechanism of NAD metabolism-related genes (NMRGs) in B-ALL relapse remains unclear. Methods: Transcriptome data (GSE3912), and single-cell sequencing data (GSE130116) of B-ALL patients were downloaded from Gene Expression Omnibus (GEO) database. NMRGs were sourced from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Further, the differentially expressed NMRGs (DE-NMRGs) were selected from the analysis between initial diagnosis and relapse B-ALL samples, which further performed functional enrichment analyses. The biomarkers were obtained through random forest (RF) algorithm and repeated cross validation. Additionally, cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was used to evaluate the immune cell differences between the initial diagnosis and relapse samples, and the correlations between biomarkers and gene markers of differential immune cells were analyzed. Furthermore, single cell RNA sequencing was conducted in the GSE130116 dataset to find key cell clusters. In addition, according to biomarkers expressions, cell clusters were categorized into high and low biomarker expression groups, and Gene Set Enrichment Analysis (GSEA) analysis was performed on them. Finally, the cell clusters with the highest expression of biomarkers were selected to exp...