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Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma

INTRODUCTION: Despite modern multimodal therapeutic regimens, the prognosis of esophageal adenocarcinoma (EAC) is still poor and there is a lack of biological markers estimating the patients’ prognosis. Fructose-1,6-biphosphatase (FBP1) is a key enzyme in gluconeogenesis and is associated with tumor...

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Autores principales: Damanakis, Alexander, Plum, Patrick Sven, Gebauer, Florian, Schröder, Wolfgang, Büttner, Reinhard, Zander, Thomas, Bruns, Christiane Josephine, Quaas, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349078/
https://www.ncbi.nlm.nih.gov/pubmed/35477823
http://dx.doi.org/10.1007/s00432-022-04025-x
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author Damanakis, Alexander
Plum, Patrick Sven
Gebauer, Florian
Schröder, Wolfgang
Büttner, Reinhard
Zander, Thomas
Bruns, Christiane Josephine
Quaas, Alexander
author_facet Damanakis, Alexander
Plum, Patrick Sven
Gebauer, Florian
Schröder, Wolfgang
Büttner, Reinhard
Zander, Thomas
Bruns, Christiane Josephine
Quaas, Alexander
author_sort Damanakis, Alexander
collection PubMed
description INTRODUCTION: Despite modern multimodal therapeutic regimens, the prognosis of esophageal adenocarcinoma (EAC) is still poor and there is a lack of biological markers estimating the patients’ prognosis. Fructose-1,6-biphosphatase (FBP1) is a key enzyme in gluconeogenesis and is associated with tumor initiation in several cancers. Therefore, this study aims to characterize its implication for EAC patients. METHODS AND MATERIALS: A total of 571 EAC patients who underwent multimodal treatment between 1999 and 2017 were analyzed for FBP1 expression using immunohistochemistry. RESULTS: 82.5% of the EACs show FBP1 expression in the tumor albeit with different intensities categorizing specimens accordingly into score 0 (no expression), score 1 (weak expression), score 2 (moderate expression) and score 3 (strong expression) (score 1 = 25.0%, score 2 = 35.9%, score 3 = 21.5%). Intratumoral FBP1 expression was significantly associated with a better prognosis (p = 0.024). This observation was particularly relevant among patients who received primary surgery without neoadjuvant treatment (p = 0.004). In multivariate analysis, elevated FBP1 expression was an independent biomarker associated with a favorable prognosis. DISCUSSION: Despite being associated with a favorable prognosis, the majority of patients with high FBP1 expression also require individualized therapy options to ensure long-term survival. Recently, it has been shown that the presence of the FBP1 protein increases the sensitivity of pancreatic cancer cells to the bromodomain and extraterminal domain (BET) inhibitor JQ1. CONCLUSION: We described for the first time the prognostic and possibly therapeutic relevance of FBP1 in EAC. The efficiency of the BET inhibitor in EAC should be verified in clinical studies and special attention should be paid to the effects of neoadjuvant therapy on FBP1 expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-022-04025-x.
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spelling pubmed-93490782022-08-05 Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma Damanakis, Alexander Plum, Patrick Sven Gebauer, Florian Schröder, Wolfgang Büttner, Reinhard Zander, Thomas Bruns, Christiane Josephine Quaas, Alexander J Cancer Res Clin Oncol Original Article – Cancer Research INTRODUCTION: Despite modern multimodal therapeutic regimens, the prognosis of esophageal adenocarcinoma (EAC) is still poor and there is a lack of biological markers estimating the patients’ prognosis. Fructose-1,6-biphosphatase (FBP1) is a key enzyme in gluconeogenesis and is associated with tumor initiation in several cancers. Therefore, this study aims to characterize its implication for EAC patients. METHODS AND MATERIALS: A total of 571 EAC patients who underwent multimodal treatment between 1999 and 2017 were analyzed for FBP1 expression using immunohistochemistry. RESULTS: 82.5% of the EACs show FBP1 expression in the tumor albeit with different intensities categorizing specimens accordingly into score 0 (no expression), score 1 (weak expression), score 2 (moderate expression) and score 3 (strong expression) (score 1 = 25.0%, score 2 = 35.9%, score 3 = 21.5%). Intratumoral FBP1 expression was significantly associated with a better prognosis (p = 0.024). This observation was particularly relevant among patients who received primary surgery without neoadjuvant treatment (p = 0.004). In multivariate analysis, elevated FBP1 expression was an independent biomarker associated with a favorable prognosis. DISCUSSION: Despite being associated with a favorable prognosis, the majority of patients with high FBP1 expression also require individualized therapy options to ensure long-term survival. Recently, it has been shown that the presence of the FBP1 protein increases the sensitivity of pancreatic cancer cells to the bromodomain and extraterminal domain (BET) inhibitor JQ1. CONCLUSION: We described for the first time the prognostic and possibly therapeutic relevance of FBP1 in EAC. The efficiency of the BET inhibitor in EAC should be verified in clinical studies and special attention should be paid to the effects of neoadjuvant therapy on FBP1 expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-022-04025-x. Springer Berlin Heidelberg 2022-04-27 2022 /pmc/articles/PMC9349078/ /pubmed/35477823 http://dx.doi.org/10.1007/s00432-022-04025-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article – Cancer Research
Damanakis, Alexander
Plum, Patrick Sven
Gebauer, Florian
Schröder, Wolfgang
Büttner, Reinhard
Zander, Thomas
Bruns, Christiane Josephine
Quaas, Alexander
Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma
title Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma
title_full Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma
title_fullStr Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma
title_full_unstemmed Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma
title_short Fructose-1,6-bisphosphatase 1 (FBP1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma
title_sort fructose-1,6-bisphosphatase 1 (fbp1) is an independent biomarker associated with a favorable prognosis in esophageal adenocarcinoma
topic Original Article – Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349078/
https://www.ncbi.nlm.nih.gov/pubmed/35477823
http://dx.doi.org/10.1007/s00432-022-04025-x
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