PMID- 30901224
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1535-3907 (Electronic)
IS  - 1535-3893 (Linking)
VI  - 18
IP  - 5
DP  - 2019 May 3
TI  - Significant Down-Regulation of Urea Cycle Generates Clinically Relevant Proteomic 
      Signature in Hepatocellular Carcinoma Patients with Macrovascular Invasion.
PG  - 2032-2044
LID - 10.1021/acs.jproteome.8b00921 [doi]
AB  - Vascular invasion is considered as the critical risk factor of hepatocellular 
      carcinoma (HCC). To reveal the molecular mechanisms underlying macrovascular 
      invasion (MaVI) in HCC, we performed an iTRAQ based proteomic study to identify 
      notably dysregulated proteins from eight HCC patients with differential vascular 
      invasion and further confirmed them in the other 53 HCC patients. Forty-seven 
      proteins were found significantly down-regulated in HCC with MaVI. More 
      importantly, 30 of them were not changed in HCC without MaVI. Gene ontology 
      analysis of these 47 proteins shows the top three enriched biological processes 
      are urea cycle, gluconeogenesis, and arginine biosynthetic process. We validated 
      nine remarkably dysregulated candidates in HCC patients with MaVI by Western blot 
      including eight down-regulated proteins (CPS1, ASS1, ASL, ARG1, BHMT, DMGDH, 
      Annexin A6, and CES1) and one up-regulated protein (CKAP4). Furthermore, 
      dysregulation of CPS1, ASL, and ARG1, key enzymes involved in urea cycle, 
      together with Annexin A6 and CES1, major proteins in regulating cholesterol 
      homeostasis and fatty acid ester metabolism, was verified using 
      immunohistochemical staining. The significant down-regulation of urea cycle 
      generates clinically relevant proteomic signature in HCC patients with 
      macrovascular invasion, which may provide possible insights into the molecular 
      mechanisms of metastasis and new therapeutic targets of HCC.
FAU - Cao, Yin
AU  - Cao Y
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
AD  - Department of Hepatobiliary Surgery , The Affiliated Drum Tower Hospital of 
      Nanjing University Medical School , 321 Zhongshan Road , Gulou District, Nanjing 
      210008 , China.
FAU - Ding, WenWen
AU  - Ding W
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
FAU - Zhang, JingZi
AU  - Zhang J
AUID- ORCID: 0000-0002-7190-6243
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
FAU - Gao, Qi
AU  - Gao Q
AUID- ORCID: 0000-0002-6342-2804
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
FAU - Yang, HaoXiang
AU  - Yang H
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
FAU - Cao, WangSen
AU  - Cao W
AUID- ORCID: 0000-0001-6209-3482
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
FAU - Wang, ZhongXia
AU  - Wang Z
AUID- ORCID: 0000-0001-6333-1999
AD  - Department of Hepatobiliary Surgery , The Affiliated Drum Tower Hospital of 
      Nanjing University Medical School , 321 Zhongshan Road , Gulou District, Nanjing 
      210008 , China.
FAU - Fang, Lei
AU  - Fang L
AUID- ORCID: 0000-0002-2582-4845
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
FAU - Du, RongHui
AU  - Du R
AD  - Jiangsu Key Laboratory of Molecular Medicine , Medical School of Nanjing 
      University , 22 Hankou Road , Gulou District, Nanjing 210093 , China.
LA  - eng
PT  - Journal Article
DEP - 20190329
PL  - United States
TA  - J Proteome Res
JT  - Journal of proteome research
JID - 101128775
RN  - 0 (Fatty Acids)
RN  - 0 (Neoplasm Proteins)
RN  - 8W8T17847W (Urea)
RN  - 94ZLA3W45F (Arginine)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arginine/metabolism
MH  - Blood Vessels/*metabolism/pathology
MH  - Carcinoma, Hepatocellular/*genetics/metabolism/mortality/pathology
MH  - Cholesterol/metabolism
MH  - Fatty Acids/metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gene Ontology
MH  - Gluconeogenesis/genetics
MH  - Humans
MH  - Liver/metabolism/pathology
MH  - Liver Neoplasms/*genetics/metabolism/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Annotation
MH  - Neoplasm Invasiveness
MH  - Neoplasm Proteins/*genetics/metabolism
MH  - Neoplasm Staging
MH  - Proteomics/methods
MH  - Urea/*metabolism
OTO - NOTNLM
OT  - HCC
OT  - iTRAQ
OT  - macorvascular invasion
OT  - molecular mechanisms
OT  - proteomic signature
OT  - urea cycle
EDAT- 2019/03/23 06:00
MHDA- 2020/06/02 06:00
CRDT- 2019/03/23 06:00
PHST- 2019/03/23 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2019/03/23 06:00 [entrez]
AID - 10.1021/acs.jproteome.8b00921 [doi]
PST - ppublish
SO  - J Proteome Res. 2019 May 3;18(5):2032-2044. doi: 10.1021/acs.jproteome.8b00921. 
      Epub 2019 Mar 29.