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FGFR1 expression defines clinically distinct subtypes in pancreatic cancer

BACKGROUND: The clinical significance of fibroblast growth factor receptor 1 (FGFR1) protein expression in pancreatic cancer is largely unknown. In this study, we aimed investigate the clinical significance of FGFR1 expression in pancreatic cancer. METHODS: First, we investigated the relationship be...

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Autores principales: Haq, Farhan, Sung, You-Na, Park, Inkeun, Kayani, Mahmood Akhtar, Yousuf, Faizah, Hong, Seung-Mo, Ahn, Sung-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311038/
https://www.ncbi.nlm.nih.gov/pubmed/30593273
http://dx.doi.org/10.1186/s12967-018-1743-9
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author Haq, Farhan
Sung, You-Na
Park, Inkeun
Kayani, Mahmood Akhtar
Yousuf, Faizah
Hong, Seung-Mo
Ahn, Sung-Min
author_facet Haq, Farhan
Sung, You-Na
Park, Inkeun
Kayani, Mahmood Akhtar
Yousuf, Faizah
Hong, Seung-Mo
Ahn, Sung-Min
author_sort Haq, Farhan
collection PubMed
description BACKGROUND: The clinical significance of fibroblast growth factor receptor 1 (FGFR1) protein expression in pancreatic cancer is largely unknown. In this study, we aimed investigate the clinical significance of FGFR1 expression in pancreatic cancer. METHODS: First, we investigated the relationship between FGFR pathway gene expression and clinicopathological data in three pancreatic cancer cohorts containing 313 cases. Subsequently, to confirm the findings from the discovery cohorts, we performed immunohistochemistry (IHC) of FGFR1 protein in a validation cohort of 205 pancreatic cancer cases. RESULTS: In discovery cohort 1, FGFR1 and Klotho beta (KLB) overexpression was associated with low tumor stage (P < 0.05), low tumor grade (P < 0.05), and better overall survival. Multivariate analysis predicted FGFR1 (P < 0.05) as a prognostic factor for better overall survival. In discovery cohorts 2 and 3, only FGFR1 overexpression was associated with better overall survival (P < 0.05). In the validation cohort, there were 15.7% and 61% strong and weak/moderate FGFR1-positive cases, respectively. FGFR1-positive cases showed better overall survival than FGFR1-negative cases (P < 0.05). Furthermore, multivariate analysis revealed FGFR1 positivity as an independent prognostic factor for better overall survival in pancreatic cancer patients (hazard ratio 0.677, 95% confidence interval 0.471–0.972, P = 0.035). CONCLUSIONS: FGFR1 expression, as estimated by IHC, may be used to define clinically distinct subtypes in pancreatic cancer. Moreover, FGFR1-based subclassification of pancreatic cancer may lead to new therapeutic approaches for the FGFR1-positive subtype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1743-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-63110382019-01-07 FGFR1 expression defines clinically distinct subtypes in pancreatic cancer Haq, Farhan Sung, You-Na Park, Inkeun Kayani, Mahmood Akhtar Yousuf, Faizah Hong, Seung-Mo Ahn, Sung-Min J Transl Med Research BACKGROUND: The clinical significance of fibroblast growth factor receptor 1 (FGFR1) protein expression in pancreatic cancer is largely unknown. In this study, we aimed investigate the clinical significance of FGFR1 expression in pancreatic cancer. METHODS: First, we investigated the relationship between FGFR pathway gene expression and clinicopathological data in three pancreatic cancer cohorts containing 313 cases. Subsequently, to confirm the findings from the discovery cohorts, we performed immunohistochemistry (IHC) of FGFR1 protein in a validation cohort of 205 pancreatic cancer cases. RESULTS: In discovery cohort 1, FGFR1 and Klotho beta (KLB) overexpression was associated with low tumor stage (P < 0.05), low tumor grade (P < 0.05), and better overall survival. Multivariate analysis predicted FGFR1 (P < 0.05) as a prognostic factor for better overall survival. In discovery cohorts 2 and 3, only FGFR1 overexpression was associated with better overall survival (P < 0.05). In the validation cohort, there were 15.7% and 61% strong and weak/moderate FGFR1-positive cases, respectively. FGFR1-positive cases showed better overall survival than FGFR1-negative cases (P < 0.05). Furthermore, multivariate analysis revealed FGFR1 positivity as an independent prognostic factor for better overall survival in pancreatic cancer patients (hazard ratio 0.677, 95% confidence interval 0.471–0.972, P = 0.035). CONCLUSIONS: FGFR1 expression, as estimated by IHC, may be used to define clinically distinct subtypes in pancreatic cancer. Moreover, FGFR1-based subclassification of pancreatic cancer may lead to new therapeutic approaches for the FGFR1-positive subtype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1743-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-28 /pmc/articles/PMC6311038/ /pubmed/30593273 http://dx.doi.org/10.1186/s12967-018-1743-9 Text en © The Author(s) 2018 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
Haq, Farhan
Sung, You-Na
Park, Inkeun
Kayani, Mahmood Akhtar
Yousuf, Faizah
Hong, Seung-Mo
Ahn, Sung-Min
FGFR1 expression defines clinically distinct subtypes in pancreatic cancer
title FGFR1 expression defines clinically distinct subtypes in pancreatic cancer
title_full FGFR1 expression defines clinically distinct subtypes in pancreatic cancer
title_fullStr FGFR1 expression defines clinically distinct subtypes in pancreatic cancer
title_full_unstemmed FGFR1 expression defines clinically distinct subtypes in pancreatic cancer
title_short FGFR1 expression defines clinically distinct subtypes in pancreatic cancer
title_sort fgfr1 expression defines clinically distinct subtypes in pancreatic cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311038/
https://www.ncbi.nlm.nih.gov/pubmed/30593273
http://dx.doi.org/10.1186/s12967-018-1743-9
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