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Published in: Esophagus 1/2014

01-01-2014 | Original Article

Expression analysis of fibroblast growth factor receptor-like 1 (FGFRL1) in esophageal squamous cell carcinoma

Authors: Yutaka Shimada, Tomoyuki Okumura, Takuya Nagata, Isaya Hashimoto, Shigeaki Sawada, Toru Yoshida, Junya Fukuoka, Kazuharu Shimizu, Kazuhiro Tsukada

Published in: Esophagus | Issue 1/2014

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Abstract

Background

We previously reported that microRNA-210 regulates cancer cell proliferation by targeting fibroblast growth factor receptor-like 1 (FGFRL1) in esophageal squamous cell carcinoma (ESCC). In order to clarify the role of FGFRL1 in ESCC, we evaluated FGFRL1 expression by tissue microarray and compared it with the clinicopathological factors of patients.

Materials and methods

Sixty-nine specimens of ESCC were obtained from patients who underwent an operation from 1990 to 2008. The patients consisted of 62 males and 7 females. Average age was 64.1 years old. The TNM stages of the patients were as follows: stage I, 7 patients; stage IIA, 10; stage IIB, 10; stage III, 35; stage IV, 7. After careful examination by two independent researchers, the immunohistochemical results for these patients were scored according to intensity and distribution.

Results

Among the 69 patients with ESCC, 56 patients (81 %) were FGFRL1 positive and 13 patients were FGFRL1 negative. FGFRL1 positivity was associated with lymph node metastasis (p = 0.004) and tended to be associated with the depth of the tumor (p = 0.089). As a result, the prognosis of the FGFRL1-positive patients was significantly worse than that of the FGFRL1-negative patients (logrank p = 0.0311). However, FGFRL1 expression was not an independent prognostic factor for the patients.

Conclusion

FGFRL1 expression was associated with both lymph node metastasis and tumor growth in the patients with ESCC.
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.
2.
go back to reference Rice TW, Rusch VW, Apperson-Hansen C, Allen MS, Chen LQ, Hunter JG, Kesler KA, Law S, Lerut TEMR, Reed CE, Salo JA, Scott WJ, Swisher SG, Watson TJ, Blackstone EH. Worldwide esophageal cancer collaboration. Dis Esophagus. 2009;22:1–8.PubMedCrossRef Rice TW, Rusch VW, Apperson-Hansen C, Allen MS, Chen LQ, Hunter JG, Kesler KA, Law S, Lerut TEMR, Reed CE, Salo JA, Scott WJ, Swisher SG, Watson TJ, Blackstone EH. Worldwide esophageal cancer collaboration. Dis Esophagus. 2009;22:1–8.PubMedCrossRef
3.
go back to reference Ozawa S, Tachimori Y, Baba H, Fujishiro M, Matsubara H, Numasaki H, Oyama T, Shinoda M, Takeuchi H, Teshima T, Udagawa H, Uno T, Barron JP. Comprehensive registry of esophageal cancer in Japan, 2004. Esophagus. 2012;9:75–98.CrossRef Ozawa S, Tachimori Y, Baba H, Fujishiro M, Matsubara H, Numasaki H, Oyama T, Shinoda M, Takeuchi H, Teshima T, Udagawa H, Uno T, Barron JP. Comprehensive registry of esophageal cancer in Japan, 2004. Esophagus. 2012;9:75–98.CrossRef
4.
go back to reference Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G. MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem. 2011;286:420–8.PubMedCrossRef Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G. MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem. 2011;286:420–8.PubMedCrossRef
5.
go back to reference Zhuang L, Falquet L, Trueb B. Genome-wide comparison of FGFRL1 with structurally related surface receptors. Exp Ther Med. 2010;1:161–8.PubMedCentralPubMed Zhuang L, Falquet L, Trueb B. Genome-wide comparison of FGFRL1 with structurally related surface receptors. Exp Ther Med. 2010;1:161–8.PubMedCentralPubMed
6.
go back to reference Trueb B. Biology of FGFRL1, the fifth fibroblast growth factor receptor. Cell Mol Life Sci. 2011;68:951–64.PubMedCrossRef Trueb B. Biology of FGFRL1, the fifth fibroblast growth factor receptor. Cell Mol Life Sci. 2011;68:951–64.PubMedCrossRef
7.
go back to reference Shimada Y, Okumura T, Sekine S, Moriyama M, Sawada S, Matsui K, Yoshioka I, Hojo S, Yoshida T, Nagata T, Fukuoka J, Tsukada K. Expression analysis of iPS cell-inductive genes in esophageal squamous cell carcinoma by tissue microarray. Anticancer Res. 2012;32:5507–14. Shimada Y, Okumura T, Sekine S, Moriyama M, Sawada S, Matsui K, Yoshioka I, Hojo S, Yoshida T, Nagata T, Fukuoka J, Tsukada K. Expression analysis of iPS cell-inductive genes in esophageal squamous cell carcinoma by tissue microarray. Anticancer Res. 2012;32:5507–14.
8.
go back to reference Semrad TJ, Mack PC. Fibroblast growth factor signaling in non-small-cell lung cancer. Clin Lung Cancer. 2012;13:90–5.PubMedCrossRef Semrad TJ, Mack PC. Fibroblast growth factor signaling in non-small-cell lung cancer. Clin Lung Cancer. 2012;13:90–5.PubMedCrossRef
9.
go back to reference Blanckaert VD, Hebbar M, Louchez MM, Vilain MO, Schelling ME, Peyrat JP. Basic fibroblast growth factor receptors and their prognostic value in human breast cancer. Clin Cancer Res. 1998;4:2939–47.PubMed Blanckaert VD, Hebbar M, Louchez MM, Vilain MO, Schelling ME, Peyrat JP. Basic fibroblast growth factor receptors and their prognostic value in human breast cancer. Clin Cancer Res. 1998;4:2939–47.PubMed
10.
go back to reference Cole C, Lau S, Backen A, Clamp A, Rushton G, Dive C, Hodgkinson C, McVey R, Kitchener H, Jayson GC. Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer. Cancer Biol Ther. 2010;10:495–504.PubMedCrossRef Cole C, Lau S, Backen A, Clamp A, Rushton G, Dive C, Hodgkinson C, McVey R, Kitchener H, Jayson GC. Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer. Cancer Biol Ther. 2010;10:495–504.PubMedCrossRef
11.
go back to reference Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA. Expression of bFGF/FGFR-1 and vascular proliferation related to clinicopathologic features and tumor progress in localized prostate cancer. Virchows Arch. 2006;448:68–74.PubMedCrossRef Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA. Expression of bFGF/FGFR-1 and vascular proliferation related to clinicopathologic features and tumor progress in localized prostate cancer. Virchows Arch. 2006;448:68–74.PubMedCrossRef
12.
go back to reference Tomlinson DC, Lamont FR, Shnyder SD, Knowles MA. Fibroblast growth factor receptor 1 promotes proliferation and survival via activation of the mitogen-activated protein kinase pathway in bladder cancer. Cancer Res. 2009;69:4613–20.PubMedCentralPubMedCrossRef Tomlinson DC, Lamont FR, Shnyder SD, Knowles MA. Fibroblast growth factor receptor 1 promotes proliferation and survival via activation of the mitogen-activated protein kinase pathway in bladder cancer. Cancer Res. 2009;69:4613–20.PubMedCentralPubMedCrossRef
13.
go back to reference Wagner M, Lopez ME, Cahn M, Korc M. Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo. Gastroenterology. 1998;114:798–807.PubMedCrossRef Wagner M, Lopez ME, Cahn M, Korc M. Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo. Gastroenterology. 1998;114:798–807.PubMedCrossRef
14.
go back to reference Marshall ME, Hinz TK, Kono SA, Singleton KR, Bichon B, Ware KE, Marek L, Frederick BA, Raben D, Heasley LE. Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin Cancer Res. 2011;17:5016–25. Marshall ME, Hinz TK, Kono SA, Singleton KR, Bichon B, Ware KE, Marek L, Frederick BA, Raben D, Heasley LE. Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin Cancer Res. 2011;17:5016–25.
15.
go back to reference Sugiura K, Ozawa S, Kitagawa Y, Ueda M, Kitajima M. Co-expression of aFGF and FGFR-1 is predictive of a poor prognosis in patients with esophageal squamous cell carcinoma. Oncol Rep. 2007;17:557–64.PubMed Sugiura K, Ozawa S, Kitagawa Y, Ueda M, Kitajima M. Co-expression of aFGF and FGFR-1 is predictive of a poor prognosis in patients with esophageal squamous cell carcinoma. Oncol Rep. 2007;17:557–64.PubMed
16.
go back to reference Zhang C, Fu L, Fu J, Hu L, Yang H, Rong TH, et al. Fibroblast growth factor receptor 2-positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma. Clin Cancer Res. 2009;15:4017–27.PubMedCrossRef Zhang C, Fu L, Fu J, Hu L, Yang H, Rong TH, et al. Fibroblast growth factor receptor 2-positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma. Clin Cancer Res. 2009;15:4017–27.PubMedCrossRef
17.
go back to reference Sleeman M, Fraser J, McDonald M, Yuan S, White D, Grandison P, Kumble K, Watson JD, Murison JG. Identification of a new fibroblast growth factor receptor, FGFR5. Gene. 2001;271:171–82.PubMedCrossRef Sleeman M, Fraser J, McDonald M, Yuan S, White D, Grandison P, Kumble K, Watson JD, Murison JG. Identification of a new fibroblast growth factor receptor, FGFR5. Gene. 2001;271:171–82.PubMedCrossRef
18.
go back to reference Bertrand S, Somorjai I, Garcia-Fernandez J, Lamonerie T, Escriva H. FGFRL1 is a neglected putative actor of the FGF signalling pathway present in all major metazoan phyla. BMC Evol Biol. 2009;9:226.PubMedCentralPubMedCrossRef Bertrand S, Somorjai I, Garcia-Fernandez J, Lamonerie T, Escriva H. FGFRL1 is a neglected putative actor of the FGF signalling pathway present in all major metazoan phyla. BMC Evol Biol. 2009;9:226.PubMedCentralPubMedCrossRef
19.
go back to reference Steinberg F, Zhuang L, Beyeler M, Kälin RE, Mullis PE, Brändli AW, Trueb B. The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs), and antagonizes FGF signaling in Xenopus embryos. J Biol Chem. 2010;285:2193–202.PubMedCrossRef Steinberg F, Zhuang L, Beyeler M, Kälin RE, Mullis PE, Brändli AW, Trueb B. The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs), and antagonizes FGF signaling in Xenopus embryos. J Biol Chem. 2010;285:2193–202.PubMedCrossRef
20.
go back to reference LopezJimenez N, Gerber S, Popovici V, Mirza S, Copren K, Ta L, Shaw GM, Trueb B, Slavotinek AM. Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm. Hum Genet. 2010;127:325–36.PubMedCentralPubMedCrossRef LopezJimenez N, Gerber S, Popovici V, Mirza S, Copren K, Ta L, Shaw GM, Trueb B, Slavotinek AM. Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm. Hum Genet. 2010;127:325–36.PubMedCentralPubMedCrossRef
21.
go back to reference Gerber SD, Amann R, Wyder S, Trueb B. Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling. PLoS One. 2012;7:e33457.PubMedCentralPubMedCrossRef Gerber SD, Amann R, Wyder S, Trueb B. Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling. PLoS One. 2012;7:e33457.PubMedCentralPubMedCrossRef
22.
go back to reference Schild C, Trueb B. Aberrant expression of FGFRL1, a novel FGF receptor, in ovarian tumors. Int J Mol Med. 2005;16:1169–73.PubMed Schild C, Trueb B. Aberrant expression of FGFRL1, a novel FGF receptor, in ovarian tumors. Int J Mol Med. 2005;16:1169–73.PubMed
Metadata
Title
Expression analysis of fibroblast growth factor receptor-like 1 (FGFRL1) in esophageal squamous cell carcinoma
Authors
Yutaka Shimada
Tomoyuki Okumura
Takuya Nagata
Isaya Hashimoto
Shigeaki Sawada
Toru Yoshida
Junya Fukuoka
Kazuharu Shimizu
Kazuhiro Tsukada
Publication date
01-01-2014
Publisher
Springer Japan
Published in
Esophagus / Issue 1/2014
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-013-0394-4

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