The Prognostic Impact of Leucine-Rich α-2-Glycoprotein-1 in Cholangiocarcinoma and Its Association With the IL-6/TGF-β1 Axis.
Aged
Bile Duct Neoplasms
/ blood supply
Bile Ducts, Intrahepatic
/ blood supply
Cholangiocarcinoma
/ blood supply
Cholecystectomy
Disease-Free Survival
Epithelial-Mesenchymal Transition
Female
Follow-Up Studies
Glycoproteins
/ analysis
Humans
Interleukin-6
/ analysis
Kaplan-Meier Estimate
Male
Microvessels
/ pathology
Middle Aged
Neoplasm Recurrence, Local
/ epidemiology
Postoperative Period
Prognosis
Retrospective Studies
Transforming Growth Factor beta1
/ analysis
Up-Regulation
Inflammatory cytokines
Intrahepatic cholangiocarcinoma
Metastasis
Journal
The Journal of surgical research
ISSN: 1095-8673
Titre abrégé: J Surg Res
Pays: United States
ID NLM: 0376340
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
26
09
2019
revised:
28
01
2020
accepted:
09
03
2020
pubmed:
13
4
2020
medline:
10
9
2020
entrez:
13
4
2020
Statut:
ppublish
Résumé
Leucine-rich α-2-glycoprotein-1 (LRG) has been found to participate in the development of various cancers through its involvement in TGF-β1-induced epithelial-mesenchymal transition (EMT) and/or angiogenesis and can be induced by inflammatory cytokines, such as IL-6. As we previously showed the implication of IL-6/TGF-β axis in EMT of cholangiocarcinoma cells, we herein explored the prognostic impact of LRG in postoperative intrahepatic cholangiocarcinoma (ICC) and assessed the association between tumor LRG and factors such as TGF-β1, IL-6, and the tumor microvessel density. We determined the expression of LRG, IL-6, TGF-β1, and CD31 in cancer tissues from 50 ICC patients by immunohistochemistry and analyzed their association with the prognosis. The LRG expression was closely associated with recurrence-free survival (RFS) and overall survival (OS) in postoperative ICC. A multivariate Cox regression model indicated that LRG as an independently associated with poor RFS (hazard ratio = 2.4339, P = 0.0354) and OS (hazard ratio = 2.8892, P = 0.0268). The LRG expression was significantly associated with the expression of TGF-β1 (P = 0.0003) and IL-6 (P = 0.0164). The upregulation of LRG in tumors was an independent prognostic factor in patients with postoperative ICC. LRG was closely associated with the TGF-β1 expression and seems to be an important member of the IL-6/TGF-β1 axis.
Sections du résumé
BACKGROUND
Leucine-rich α-2-glycoprotein-1 (LRG) has been found to participate in the development of various cancers through its involvement in TGF-β1-induced epithelial-mesenchymal transition (EMT) and/or angiogenesis and can be induced by inflammatory cytokines, such as IL-6. As we previously showed the implication of IL-6/TGF-β axis in EMT of cholangiocarcinoma cells, we herein explored the prognostic impact of LRG in postoperative intrahepatic cholangiocarcinoma (ICC) and assessed the association between tumor LRG and factors such as TGF-β1, IL-6, and the tumor microvessel density.
METHODS
We determined the expression of LRG, IL-6, TGF-β1, and CD31 in cancer tissues from 50 ICC patients by immunohistochemistry and analyzed their association with the prognosis.
RESULTS
The LRG expression was closely associated with recurrence-free survival (RFS) and overall survival (OS) in postoperative ICC. A multivariate Cox regression model indicated that LRG as an independently associated with poor RFS (hazard ratio = 2.4339, P = 0.0354) and OS (hazard ratio = 2.8892, P = 0.0268). The LRG expression was significantly associated with the expression of TGF-β1 (P = 0.0003) and IL-6 (P = 0.0164).
CONCLUSIONS
The upregulation of LRG in tumors was an independent prognostic factor in patients with postoperative ICC. LRG was closely associated with the TGF-β1 expression and seems to be an important member of the IL-6/TGF-β1 axis.
Identifiants
pubmed: 32278969
pii: S0022-4804(20)30138-4
doi: 10.1016/j.jss.2020.03.018
pii:
doi:
Substances chimiques
Glycoproteins
0
IL6 protein, human
0
Interleukin-6
0
LRG1 protein, human
0
TGFB1 protein, human
0
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
147-155Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.