PMID- 31897234
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231112
IS  - 1837-9664 (Print)
IS  - 1837-9664 (Electronic)
IS  - 1837-9664 (Linking)
VI  - 11
IP  - 2
DP  - 2020
TI  - TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung 
      Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of 
      Functional Assay.
PG  - 388-402
LID - 10.7150/jca.31636 [doi]
AB  - Objective: Bone metastasis from patients with advanced lung adenocarcinoma (LAC) 
      is a very serious complication. To better understand the molecular mechanism, our 
      current study sheds light on identification of hub genes mediating bone 
      metastatic spread by combining bioinformatic analysis with functional 
      verification. Methods: First, we downloaded a lung adenocarcinoma dataset 
      (GSE76194) from Gene Expression Omnibus, analyzed differentially expressed genes 
      (DEGs) through Limma package in R software and constructed a protein-protein 
      interaction network. Based on that preliminary data, we further performed modular 
      and topological analysis using Cystoscope to obtain biological connected genes. 
      Through literature searching and performing mRNA expression analysis on the other 
      independent public dataset (GSE10799), we finally focused on TBX2. Functional 
      effects of TBX2 were performed in tumorigenicity assays including migration and 
      invasion assays, cell proliferation assay, and cell cycle assay. In addition, 
      mechanically, we found enriched pathways related to bone metastasis using Gene 
      Set Enrichment Analysis (GSEA) and validated our results by western blot. Result: 
      A total of 1132 significant genes were sorted initially. We selected common 
      significant genes (log FC>2; p<0.01) from both the biological network data and 
      microarray data. In total, 44 such genes were identified. we found TBX2, along 
      with 10 other genes, to be reported with relevance to bone metastasis in other 
      cancer types. Moreover, TBX2 showed significantly higher expression levels in 
      patients that were found positive for metastasis to bone marrow compared to 
      patients that did not exhibit this type of metastasis in the other separated 
      cohort (GSE10799). Thus, we finally focused on TBX2. We found that TBX2 had 
      detectable expression in LAC cell lines and silencing endogenous TBX2 expression 
      in A549 and H1299 cell lines markedly suppressed migration and invasion, cell 
      proliferation and arrested cell-cycle. Pathway enrichment analyses suggested that 
      TBX2 drove LAC oncogenesis and metastasis through various pathways with 
      epithelial mesenchymal transition (EMT) figuring prominently in the bone 
      metastatic group, which was evidenced by western blot. Conclusion: Collectively, 
      TBX2 plays as a potential predictor of bone metastasis from LAC, yielding a 
      better promise view towards "driver" gene responsible for bone metastasis.
CI  - (c) The author(s).
FAU - Yu, Huajian
AU  - Yu H
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
FAU - Zhao, Fangyu
AU  - Zhao F
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
FAU - Li, Jing
AU  - Li J
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
FAU - Zhu, Kechao
AU  - Zhu K
AD  - Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai, China.
FAU - Lin, Hechun
AU  - Lin H
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
FAU - Pan, Zhen
AU  - Pan Z
AD  - Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth 
      People's Hospital, Shanghai, China.
FAU - Zhu, Miaoxin
AU  - Zhu M
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
FAU - Yao, Ming
AU  - Yao M
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
FAU - Yan, Mingxia
AU  - Yan M
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 
      China.
AD  - Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20200101
PL  - Australia
TA  - J Cancer
JT  - Journal of Cancer
JID - 101535920
PMC - PMC6930436
OTO - NOTNLM
OT  - Bone metastasis
OT  - Integrated bioinformatics analysis
OT  - Lung adenocarcinoma.
OT  - TBX2
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/01/04 06:00
MHDA- 2020/01/04 06:01
PMCR- 2020/01/01
CRDT- 2020/01/04 06:00
PHST- 2018/11/19 00:00 [received]
PHST- 2019/10/07 00:00 [accepted]
PHST- 2020/01/04 06:00 [entrez]
PHST- 2020/01/04 06:00 [pubmed]
PHST- 2020/01/04 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - jcav11p0388 [pii]
AID - 10.7150/jca.31636 [doi]
PST - epublish
SO  - J Cancer. 2020 Jan 1;11(2):388-402. doi: 10.7150/jca.31636. eCollection 2020.