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Bioinformatics analyses of differentially expressed genes associated with bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma.

Sun J, Wen X, Jin F, Li Y, Hu J, Sun Y - Onco Targets Ther (2015)

Bottom Line: Differentially expressed genes (DEGs) from eleven patients with ONJ resulting from MM treated with BPs (ONJBPs) and ten MM patients without ONJ treated with BPs (MMBPs) were analyzed.Moreover, the GO terms enriched by the up-regulated DEGs were associated with misfolded proteins, and the down-regulated DEGs were associated with immune responses.DEGs such as TNF, ILB1, DDX5, and XBP1 may be the potential targets of ONJ treatment.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, People's Republic of China.

ABSTRACT

Purpose: This study aimed to explore the molecular mechanisms associated with bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma (MM).

Methods: The gene expression profile GSE7116 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) from eleven patients with ONJ resulting from MM treated with BPs (ONJBPs) and ten MM patients without ONJ treated with BPs (MMBPs) were analyzed. Gene ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by functional annotation and protein-protein interaction network construction. Finally, sub-network modules were constructed and analyzed.

Results: A total of 166 up- and 473 down-regulated DEGs were identified. The up-regulated DEGs were enriched in pathways related to cancer, and the down-regulated DEGs were enriched in pathways related to the immune system. Moreover, the GO terms enriched by the up-regulated DEGs were associated with misfolded proteins, and the down-regulated DEGs were associated with immune responses. After functional annotation, 16 transcription factors were identified, including X-box binding protein 1 (XBP1). In protein-protein interaction network analysis, tumor necrosis factor (TNF) and interleukin 1, beta (IL1B) had higher connectivity degrees. Among the constructed sub-network modules, module 1 was the best one, and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) was a hub gene. The DEGs in module 1 were mainly enriched in GO terms related to RNA splicing.

Conclusion: DEGs of ONJ were mainly enriched in pathways related to the immune system and RNA splicing. DEGs such as TNF, ILB1, DDX5, and XBP1 may be the potential targets of ONJ treatment.

No MeSH data available.


Related in: MedlinePlus

The constructed protein–protein interaction network of differentially expressed genes (DEGs).Notes: Red, up-regulated DEGs; green, down-regulated DEGs.
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f1-ott-8-2681: The constructed protein–protein interaction network of differentially expressed genes (DEGs).Notes: Red, up-regulated DEGs; green, down-regulated DEGs.

Mentions: Based on the STRING database, PPI networks with a degree of more than 15 were then constructed using Cytoscape, and networks with 281 nodes and 643 edges were obtained (Figure 1). Fifteen nodes were selected as hub genes with a degree >15, including mitogen-activated protein kinase 1 (degree =30), tumor necrosis factor (TNF, degree =20), and interleukin 1, beta (IL1B, degree =17).


Bioinformatics analyses of differentially expressed genes associated with bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma.

Sun J, Wen X, Jin F, Li Y, Hu J, Sun Y - Onco Targets Ther (2015)

The constructed protein–protein interaction network of differentially expressed genes (DEGs).Notes: Red, up-regulated DEGs; green, down-regulated DEGs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590669&req=5

f1-ott-8-2681: The constructed protein–protein interaction network of differentially expressed genes (DEGs).Notes: Red, up-regulated DEGs; green, down-regulated DEGs.
Mentions: Based on the STRING database, PPI networks with a degree of more than 15 were then constructed using Cytoscape, and networks with 281 nodes and 643 edges were obtained (Figure 1). Fifteen nodes were selected as hub genes with a degree >15, including mitogen-activated protein kinase 1 (degree =30), tumor necrosis factor (TNF, degree =20), and interleukin 1, beta (IL1B, degree =17).

Bottom Line: Differentially expressed genes (DEGs) from eleven patients with ONJ resulting from MM treated with BPs (ONJBPs) and ten MM patients without ONJ treated with BPs (MMBPs) were analyzed.Moreover, the GO terms enriched by the up-regulated DEGs were associated with misfolded proteins, and the down-regulated DEGs were associated with immune responses.DEGs such as TNF, ILB1, DDX5, and XBP1 may be the potential targets of ONJ treatment.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, People's Republic of China.

ABSTRACT

Purpose: This study aimed to explore the molecular mechanisms associated with bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma (MM).

Methods: The gene expression profile GSE7116 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) from eleven patients with ONJ resulting from MM treated with BPs (ONJBPs) and ten MM patients without ONJ treated with BPs (MMBPs) were analyzed. Gene ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by functional annotation and protein-protein interaction network construction. Finally, sub-network modules were constructed and analyzed.

Results: A total of 166 up- and 473 down-regulated DEGs were identified. The up-regulated DEGs were enriched in pathways related to cancer, and the down-regulated DEGs were enriched in pathways related to the immune system. Moreover, the GO terms enriched by the up-regulated DEGs were associated with misfolded proteins, and the down-regulated DEGs were associated with immune responses. After functional annotation, 16 transcription factors were identified, including X-box binding protein 1 (XBP1). In protein-protein interaction network analysis, tumor necrosis factor (TNF) and interleukin 1, beta (IL1B) had higher connectivity degrees. Among the constructed sub-network modules, module 1 was the best one, and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) was a hub gene. The DEGs in module 1 were mainly enriched in GO terms related to RNA splicing.

Conclusion: DEGs of ONJ were mainly enriched in pathways related to the immune system and RNA splicing. DEGs such as TNF, ILB1, DDX5, and XBP1 may be the potential targets of ONJ treatment.

No MeSH data available.


Related in: MedlinePlus