Background: 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.
Methods: Differentially 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.
Results: HLA-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).
Conclusion: We 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 function and mechanism studies are need to investigate HLA-DPA1 as potential therapeutic target.

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On 09 Sep, 2020
On 08 Sep, 2020
Invitations sent on 08 Sep, 2020
On 08 Sep, 2020
On 08 Sep, 2020
Received 08 Sep, 2020
Received 08 Sep, 2020
On 07 Sep, 2020
On 07 Sep, 2020
Posted 01 Jul, 2020
On 24 Aug, 2020
Received 20 Aug, 2020
On 31 Jul, 2020
Received 30 Jul, 2020
On 28 Jul, 2020
Invitations sent on 15 Jul, 2020
On 21 Jun, 2020
On 20 Jun, 2020
On 20 Jun, 2020
On 19 Jun, 2020
On 09 Sep, 2020
On 08 Sep, 2020
Invitations sent on 08 Sep, 2020
On 08 Sep, 2020
On 08 Sep, 2020
Received 08 Sep, 2020
Received 08 Sep, 2020
On 07 Sep, 2020
On 07 Sep, 2020
Posted 01 Jul, 2020
On 24 Aug, 2020
Received 20 Aug, 2020
On 31 Jul, 2020
Received 30 Jul, 2020
On 28 Jul, 2020
Invitations sent on 15 Jul, 2020
On 21 Jun, 2020
On 20 Jun, 2020
On 20 Jun, 2020
On 19 Jun, 2020
Background: 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.
Methods: Differentially 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.
Results: HLA-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).
Conclusion: We 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 function and mechanism studies are need to investigate HLA-DPA1 as potential therapeutic target.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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