Abstract
BackgroundMultiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment. However, the underlying mechanisms are still far from fully understood. We took integrated bioinformatics analysis with expression profile GSE110113 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database, and screened out major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) as a hub gene related to hypoxia in MM.MethodsDifferentially expressed genes (DEGs) were filtrated with R package “limma”. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed using “clusterProfiler” package in R. Then, protein-protein interaction (PPI) network was established. Hub genes were screened out according to Maximal Clique Centrality (MCC). PrognoScan evaluated all the significant hub genes for survival analysis. ScanGEO was used for visualization of gene expression in different clinical studies. P and Cox p value < 0.05 was considered to be statistical significance.ResultsHLA-DPA1 was finally picked out as a hub gene in MM related to hypoxia. MM patients with down-regulated expression of HLA-DPA1 has statistically significantly shorter disease specific survival (DSS) (COX p = 0.005411). Based on the clinical data of GSE47552 dataset, HLA-DPA1 expression showed significantly lower in MM patients than that in healthy donors (HDs) (p = 0.017).ConclusionWe identified HLA-DPA1 as a hub gene in MM related to hypoxia. HLA-DPA1 down-regulated expression was associated with MM patients’ poor outcome. Further functional and mechanistic studies are need to investigate HLA-DPA1 as potential therapeutic target.
Highlights
Multiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment
Three subontologies including biological process (BP), molecular function (MF), and cellular component (CC) were examined in Gene Ontology (GO) analysis
Adaptive immune response pathway (p = 1.31e-10, FDR = 6.59e-07), cell adhesion molecule binding pathway (p = 0.000162, FDR = 0.104) and receptor complex pathway (p = 1.23e-05, FDR = 0.00221) were selected as the most significant pathway in each subontologies, respectively (Fig. 3a-c). According to their p values, we selected adaptive immune response for further analysis and found 65 differentially expressed genes (DEGs) was enriched in this GO term
Summary
Multiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment. We took integrated bioinformatics analysis with expression profile GSE110113 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database, and screened out major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) as a hub gene related to hypoxia in MM. Multiple myeloma (MM) is a hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities [1]. Hypoxia plays an important role in occurrence and development of MM [8, 9] and more related pathogenesis is still urgent needs to be explore for better diagnosis and treatment. Class II, DP alpha 1 (HLA-DPA1) was screened out as a hub gene associated with poor outcome of MM related to hypoxia. The findings in this study provide new insights on HLA-DPA1 as a potential biomarker for MM and more research needs to be performed
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