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Title: Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma

Abstract

Highlights: • FGFR4 is significantly related with N stage in IHCC, with T stage and TNM stage in PHCC. • FGFR4 is an independent prognostic factor in IHCC and PHCC. • FGFR4 promotes proliferation, invasion and EMT in cholangiocarinoma cell lines. • Inhibitor AP24354 can decrease proliferation, invasion and induce apoptosis of CCA. - Abstract: Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of several cancers, but the correlation between FGFR4 expression and cholangiocarcinoma (CCA) has not been well elucidated. We investigated the expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with clinicopathologic parameters and survival rate. The rate of FGFR4 higher expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41) in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC (P = 0.002) and PHCC (P = 0.019) with univariate analysis, and also identified as an independent prognostic factor in IHCC (P = 0.045) and PHCC (P = 0.049) with multivariate analysis. Additionally, with functional assays in vitro, we found FGFR4 can induce proliferation, invasion and epithelial–mesenchymal transition (EMT) of CCA cellmore » lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354 can suppress proliferation, invasion and induce apoptosis of CCA cells. In conclusion, FGFR4 expression can be identified as a significant independent prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may act as a potential therapeutic target.« less

Authors:
 [1];  [2];  [3]; ; ; ; ;  [1];  [4];  [1]
  1. Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University (China)
  2. Department of Pathology, Shandong University (China)
  3. Department of Gastrointestinal Surgery, Jinan Central Hospital (China)
  4. Department of Anatomy, Shandong University (China)
Publication Date:
OSTI Identifier:
22416324
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 446; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL MARKERS; CELL PROLIFERATION; CORRELATIONS; FIBROBLASTS; GROWTH FACTORS; IN VITRO; MULTIVARIATE ANALYSIS; NEOPLASMS; RECEPTORS; STIMULATION

Citation Formats

Xu, Yun-Fei, Yang, Xiao-Qing, Lu, Xiao-Fei, Guo, Sen, Liu, Yi, Iqbal, Mohammad, Ning, Shang-Lei, Yang, Hui, Suo, Ning, and Chen, Yu-Xin, E-mail: yxu8@bidmc.harvard.edu. Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.02.050.
Xu, Yun-Fei, Yang, Xiao-Qing, Lu, Xiao-Fei, Guo, Sen, Liu, Yi, Iqbal, Mohammad, Ning, Shang-Lei, Yang, Hui, Suo, Ning, & Chen, Yu-Xin, E-mail: yxu8@bidmc.harvard.edu. Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma. United States. doi:10.1016/J.BBRC.2014.02.050.
Xu, Yun-Fei, Yang, Xiao-Qing, Lu, Xiao-Fei, Guo, Sen, Liu, Yi, Iqbal, Mohammad, Ning, Shang-Lei, Yang, Hui, Suo, Ning, and Chen, Yu-Xin, E-mail: yxu8@bidmc.harvard.edu. Fri . "Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma". United States. doi:10.1016/J.BBRC.2014.02.050.
@article{osti_22416324,
title = {Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma},
author = {Xu, Yun-Fei and Yang, Xiao-Qing and Lu, Xiao-Fei and Guo, Sen and Liu, Yi and Iqbal, Mohammad and Ning, Shang-Lei and Yang, Hui and Suo, Ning and Chen, Yu-Xin, E-mail: yxu8@bidmc.harvard.edu},
abstractNote = {Highlights: • FGFR4 is significantly related with N stage in IHCC, with T stage and TNM stage in PHCC. • FGFR4 is an independent prognostic factor in IHCC and PHCC. • FGFR4 promotes proliferation, invasion and EMT in cholangiocarinoma cell lines. • Inhibitor AP24354 can decrease proliferation, invasion and induce apoptosis of CCA. - Abstract: Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of several cancers, but the correlation between FGFR4 expression and cholangiocarcinoma (CCA) has not been well elucidated. We investigated the expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with clinicopathologic parameters and survival rate. The rate of FGFR4 higher expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41) in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC (P = 0.002) and PHCC (P = 0.019) with univariate analysis, and also identified as an independent prognostic factor in IHCC (P = 0.045) and PHCC (P = 0.049) with multivariate analysis. Additionally, with functional assays in vitro, we found FGFR4 can induce proliferation, invasion and epithelial–mesenchymal transition (EMT) of CCA cell lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354 can suppress proliferation, invasion and induce apoptosis of CCA cells. In conclusion, FGFR4 expression can be identified as a significant independent prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may act as a potential therapeutic target.},
doi = {10.1016/J.BBRC.2014.02.050},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 446,
place = {United States},
year = {2014},
month = {3}
}