title: Bioinformatics analyses of differentially expressed genes associated with bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Jingnan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Jin
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Stanford University Medical School, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Jifan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Cardiovascular Surgery Department, First Affiliated Hospital, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Sun
keywords: bisphosphonates; differentially expressed genes; functional enrichment analysis; multiple myeloma; osteonecrosis of the jaw