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Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients

BACKGROUND: The oncogenic role of the fibroblast growth factor receptor (FGFR) has been recognized in a number of different cancer types. However, the prognostic significance of FGFRs has not been elucidated yet in cervical cancer. In the present study, we investigate the expression of FGFRs and the...

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Autores principales: Choi, Chel Hun, Chung, Joon-Yong, Kim, Jae-Hoon, Kim, Byoung-Gie, Hewitt, Stephen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859953/
https://www.ncbi.nlm.nih.gov/pubmed/27154171
http://dx.doi.org/10.1186/s12967-016-0874-0
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author Choi, Chel Hun
Chung, Joon-Yong
Kim, Jae-Hoon
Kim, Byoung-Gie
Hewitt, Stephen M.
author_facet Choi, Chel Hun
Chung, Joon-Yong
Kim, Jae-Hoon
Kim, Byoung-Gie
Hewitt, Stephen M.
author_sort Choi, Chel Hun
collection PubMed
description BACKGROUND: The oncogenic role of the fibroblast growth factor receptor (FGFR) has been recognized in a number of different cancer types. However, the prognostic significance of FGFRs has not been elucidated yet in cervical cancer. In the present study, we investigate the expression of FGFRs and their prognostic value in cervical cancer patients. METHODS: FGFR1, FGFR2, FGFR3, and FGFR4 expression was determined by immunohistochemistry in conjunction with quantitative digital image analysis of 336 formalin-fixed, paraffin-embedded cervical cancer tissues and 61 normal cervical tissues, as well as NCI60 cell microarray. Subsequently, the association between clinicopathological characteristics and patient survival was assessed. RESULTS: FGFRs proteins were differentially expressed in the NCI60 cell line panel and showed considerable correlation between protein and mRNA expression. The expression of FGFR1, FGFR2, and FGFR4 were higher in cancer tissues than in normal tissues, whereas the expression of FGFR3 was higher in normal tissues. FGFR1 was highly expressed in adeno-/adenosquamous carcinoma (P = 0.020), while FGFR2, FGFR3, and FGFR4 expression were more prominent in squamous cell carcinoma (P < 0.001, P < 0.001, and P = 0.020, respectively). FGFR2 expression was significantly higher in small sized tumors (P = 0.020). Additionally, high FGFR2 and FGFR4 were correlated with negative lymph node metastasis (P = 0.048 and P = 0.040, respectively). FGFR1, FGFR2, and FGFR3 were highly expressed in tumors without parametrial involvement (P = 0.030, P = 0.005, and P = 0.010, respectively). In survival analysis, high expressions of FGFR2, FGFR3, and FGFR4 was associated with longer disease-free survival (P = 0.006, P = 0.035, P = 0.001, respectively) and overall survival (P = 0.003, P = 0.002, P = 0.003, respectively). Notably, the co-expression of all three FGFRs was significantly associated with favorable disease-free survival (P < 0.001) and overall survival (P < 0.001), compared to the negative expressions of the three FGFRs. The prognostic significance persisted in the cox regression analysis. CONCLUSIONS: The frequent expression of members of the FGFR family in cervical cancer suggests they may have prognostic and therapeutic relevance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0874-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-48599532016-05-08 Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients Choi, Chel Hun Chung, Joon-Yong Kim, Jae-Hoon Kim, Byoung-Gie Hewitt, Stephen M. J Transl Med Research BACKGROUND: The oncogenic role of the fibroblast growth factor receptor (FGFR) has been recognized in a number of different cancer types. However, the prognostic significance of FGFRs has not been elucidated yet in cervical cancer. In the present study, we investigate the expression of FGFRs and their prognostic value in cervical cancer patients. METHODS: FGFR1, FGFR2, FGFR3, and FGFR4 expression was determined by immunohistochemistry in conjunction with quantitative digital image analysis of 336 formalin-fixed, paraffin-embedded cervical cancer tissues and 61 normal cervical tissues, as well as NCI60 cell microarray. Subsequently, the association between clinicopathological characteristics and patient survival was assessed. RESULTS: FGFRs proteins were differentially expressed in the NCI60 cell line panel and showed considerable correlation between protein and mRNA expression. The expression of FGFR1, FGFR2, and FGFR4 were higher in cancer tissues than in normal tissues, whereas the expression of FGFR3 was higher in normal tissues. FGFR1 was highly expressed in adeno-/adenosquamous carcinoma (P = 0.020), while FGFR2, FGFR3, and FGFR4 expression were more prominent in squamous cell carcinoma (P < 0.001, P < 0.001, and P = 0.020, respectively). FGFR2 expression was significantly higher in small sized tumors (P = 0.020). Additionally, high FGFR2 and FGFR4 were correlated with negative lymph node metastasis (P = 0.048 and P = 0.040, respectively). FGFR1, FGFR2, and FGFR3 were highly expressed in tumors without parametrial involvement (P = 0.030, P = 0.005, and P = 0.010, respectively). In survival analysis, high expressions of FGFR2, FGFR3, and FGFR4 was associated with longer disease-free survival (P = 0.006, P = 0.035, P = 0.001, respectively) and overall survival (P = 0.003, P = 0.002, P = 0.003, respectively). Notably, the co-expression of all three FGFRs was significantly associated with favorable disease-free survival (P < 0.001) and overall survival (P < 0.001), compared to the negative expressions of the three FGFRs. The prognostic significance persisted in the cox regression analysis. CONCLUSIONS: The frequent expression of members of the FGFR family in cervical cancer suggests they may have prognostic and therapeutic relevance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0874-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-06 /pmc/articles/PMC4859953/ /pubmed/27154171 http://dx.doi.org/10.1186/s12967-016-0874-0 Text en © Choi et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Choi, Chel Hun
Chung, Joon-Yong
Kim, Jae-Hoon
Kim, Byoung-Gie
Hewitt, Stephen M.
Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients
title Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients
title_full Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients
title_fullStr Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients
title_full_unstemmed Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients
title_short Expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients
title_sort expression of fibroblast growth factor receptor family members is associated with prognosis in early stage cervical cancer patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859953/
https://www.ncbi.nlm.nih.gov/pubmed/27154171
http://dx.doi.org/10.1186/s12967-016-0874-0
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