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Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma

Achievement of microscopic tumor clearance (R0) after pancreatic ductal adenocarcinoma (PDAC) surgery is determined by cancer biology rather than operative technique. Fibroblasts are known to play pro-cancer roles; however, a small subset was recently found to play anti-cancer roles. Therefore, we h...

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Autores principales: Katsuta, Eriko, Rashid, Omar M., Takabe, Kazuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312973/
https://www.ncbi.nlm.nih.gov/pubmed/32485981
http://dx.doi.org/10.3390/ijms21113890
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author Katsuta, Eriko
Rashid, Omar M.
Takabe, Kazuaki
author_facet Katsuta, Eriko
Rashid, Omar M.
Takabe, Kazuaki
author_sort Katsuta, Eriko
collection PubMed
description Achievement of microscopic tumor clearance (R0) after pancreatic ductal adenocarcinoma (PDAC) surgery is determined by cancer biology rather than operative technique. Fibroblasts are known to play pro-cancer roles; however, a small subset was recently found to play anti-cancer roles. Therefore, we hypothesized that intratumor fibroblasts contribute to curative resection and a better survival of PDAC. Utilizing a large, publicly available PDAC cohort, we found that fibroblast composition was associated with R0 curative resection. A high amount of fibroblasts in PDACs was significantly associated with a higher amount of mature vessels, but not with blood angiogenesis. A high amount of fibroblasts was also associated with a higher infiltration of anti-cancer immune cells, such as CD8+ T-cells and dendritic cells, together with higher inflammatory signaling, including IL2/STAT5 and IL6/JAK/STAT3 signaling. Further, the fibroblast composition was inversely associated with cancer cell composition in the bulk tumor, along with an inverse association with proliferative characteristics, such as MYC signaling and glycolysis. The patients with high-fibroblast PDACs showed an improved prognosis. In conclusion, we found that PDACs with high fibroblasts were associated with a higher R0 resection rate, resulting in a better prognosis. These findings may be due to less aggressive biology with a higher vascularity and anti-cancer immunity, and a low cancer cell component.
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spelling pubmed-73129732020-06-29 Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma Katsuta, Eriko Rashid, Omar M. Takabe, Kazuaki Int J Mol Sci Article Achievement of microscopic tumor clearance (R0) after pancreatic ductal adenocarcinoma (PDAC) surgery is determined by cancer biology rather than operative technique. Fibroblasts are known to play pro-cancer roles; however, a small subset was recently found to play anti-cancer roles. Therefore, we hypothesized that intratumor fibroblasts contribute to curative resection and a better survival of PDAC. Utilizing a large, publicly available PDAC cohort, we found that fibroblast composition was associated with R0 curative resection. A high amount of fibroblasts in PDACs was significantly associated with a higher amount of mature vessels, but not with blood angiogenesis. A high amount of fibroblasts was also associated with a higher infiltration of anti-cancer immune cells, such as CD8+ T-cells and dendritic cells, together with higher inflammatory signaling, including IL2/STAT5 and IL6/JAK/STAT3 signaling. Further, the fibroblast composition was inversely associated with cancer cell composition in the bulk tumor, along with an inverse association with proliferative characteristics, such as MYC signaling and glycolysis. The patients with high-fibroblast PDACs showed an improved prognosis. In conclusion, we found that PDACs with high fibroblasts were associated with a higher R0 resection rate, resulting in a better prognosis. These findings may be due to less aggressive biology with a higher vascularity and anti-cancer immunity, and a low cancer cell component. MDPI 2020-05-29 /pmc/articles/PMC7312973/ /pubmed/32485981 http://dx.doi.org/10.3390/ijms21113890 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Katsuta, Eriko
Rashid, Omar M.
Takabe, Kazuaki
Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma
title Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma
title_full Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma
title_fullStr Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma
title_full_unstemmed Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma
title_short Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma
title_sort fibroblasts as a biological marker for curative resection in pancreatic ductal adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312973/
https://www.ncbi.nlm.nih.gov/pubmed/32485981
http://dx.doi.org/10.3390/ijms21113890
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