PMID- 31173206
OWN - NLM
STAT- MEDLINE
DCOM- 20191213
LR  - 20231012
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 20
IP  - 2
DP  - 2019 Aug
TI  - Identification of critical genes associated with human osteosarcoma metastasis 
      based on integrated gene expression profiling.
PG  - 915-930
LID - 10.3892/mmr.2019.10323 [doi]
AB  - Osteosarcoma is the most common type of malignant bone cancer, which often 
      affects teenagers and young adults. The present study aimed to screen for 
      critical genes and microRNAs (miRNAs/miRs) involved in osteosarcoma. A total of 
      four microarray datasets (accession numbers GSE32981, GSE21257, GSE14827 and 
      GSE14359) were downloaded from the Gene Expression Omnibus database. Following 
      data preprocessing, module analysis was performed to identify the stable modules 
      using the weighted gene co‑expression network analysis (WGCNA) package. The 
      differentially expressed genes (DEGs) between metastatic samples and 
      non‑metastatic samples were screened, followed by gene co‑expression network 
      construction, and Gene Ontology function and Kyoto Encyclopedia of Genes and 
      Genomes pathway analyses. Subsequently, prognosis‑associated genes were screened 
      and a miRNA‑target gene regulatory network was constructed. Finally, the data for 
      critical genes were validated. WGCNA analysis identified six modules; blue and 
      yellow modules were significantly positively associated with osteosarcoma 
      metastasis. A total of 1,613 DEGs were screened between primary tissue samples 
      and metastatic samples. Following comparison of the genes in the two (blue and 
      yellow) modules, a total of 166 DEGs were identified (metastatic samples vs. 
      non‑metastatic samples). Functional enrichment analysis demonstrated that these 
      DEGs were mainly involved in 'defense response', 'p53 signaling pathway' and 
      'lysosome'. By utilizing the clinical information in GSE21257, 10 critical genes 
      associated with osteosarcoma prognosis were obtained, including CTP synthase 2 
      (CTPS2), tumor protein p53 inducible protein 3 (TP53I3) and solute carrier 
      family 1 member 1 (SLC1A1). In addition, hsa‑miR‑422a and hsa‑miR‑194 were 
      highlighted in the miRNA‑target gene network. Finally, matrix 
      metallopeptidase 3 (MMP3) and vascular endothelial growth factor B (VEGFB) were 
      predicted as critical genes in osteosarcoma metastasis. CTPS2, TP53I3 and SLC1A1 
      may serve major roles in osteosarcoma development, and hsa‑miR‑422a, hsa‑miR‑194, 
      MMP3 and VEGFB may be associated with osteosarcoma metastasis.
FAU - Fan, Hongwu
AU  - Fan H
AD  - Department of Orthopedics, China Japan Union Hospital of Jilin University, 
      Changchun, Jilin 130021, P.R. China.
FAU - Lu, Shan
AU  - Lu S
AD  - Department of Anesthesiology, China Japan Union Hospital of Jilin University, 
      Changchun, Jilin 130021, P.R. China.
FAU - Wang, Shengqun
AU  - Wang S
AD  - Department of Orthopedics, China Japan Union Hospital of Jilin University, 
      Changchun, Jilin 130021, P.R. China.
FAU - Zhang, Shanyong
AU  - Zhang S
AD  - Department of Spinal Surgery, The Second Hospital of Jilin University, Changchun, 
      Jilin 130041, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190603
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Excitatory Amino Acid Transporter 3)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (MIRN194 microRNA, human)
RN  - 0 (MIRN422 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (SLC1A1 protein, human)
RN  - 0 (TP53I3 protein, human)
RN  - 0 (VEGFB protein, human)
RN  - 0 (Vascular Endothelial Growth Factor B)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 6.3.- (Carbon-Nitrogen Ligases)
RN  - EC 6.3.4.2 (CTP synthetase)
SB  - IM
MH  - Bone Neoplasms/*genetics/metabolism/mortality/pathology
MH  - Carbon-Nitrogen Ligases/genetics/metabolism
MH  - Databases, Genetic
MH  - Excitatory Amino Acid Transporter 3/genetics/metabolism
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gene Ontology
MH  - *Gene Regulatory Networks
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - MicroRNAs/genetics/metabolism
MH  - Molecular Sequence Annotation
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/*genetics/metabolism
MH  - Osteosarcoma/*genetics/metabolism/mortality/pathology
MH  - Protein Interaction Mapping
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Survival Analysis
MH  - Vascular Endothelial Growth Factor B/genetics/metabolism
PMC - PMC6625205
EDAT- 2019/06/08 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/06/03
CRDT- 2019/06/08 06:00
PHST- 2018/07/04 00:00 [received]
PHST- 2019/02/13 00:00 [accepted]
PHST- 2019/06/08 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/06/08 06:00 [entrez]
PHST- 2019/06/03 00:00 [pmc-release]
AID - mmr-20-02-0915 [pii]
AID - 10.3892/mmr.2019.10323 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Aug;20(2):915-930. doi: 10.3892/mmr.2019.10323. Epub 2019 Jun 
      3.