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Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer

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Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer. / Bronsert, Peter; Kohler, Ilona; Timme, Sylvia; Kiefer, Selina; Werner, Martin; Schilling, Oliver; Vashist, Yogesh; Makowiec, Frank; Brabletz, Thomas; Hopt, Ulrich T; Bausch, Dirk; Kulemann, Birte; Keck, Tobias; Wellner, Ulrich F.

in: SURGERY, Jahrgang 156, Nr. 1, 07.2014, S. 97-108.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Bronsert, P, Kohler, I, Timme, S, Kiefer, S, Werner, M, Schilling, O, Vashist, Y, Makowiec, F, Brabletz, T, Hopt, UT, Bausch, D, Kulemann, B, Keck, T & Wellner, UF 2014, 'Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer', SURGERY, Jg. 156, Nr. 1, S. 97-108. https://doi.org/10.1016/j.surg.2014.02.018

APA

Bronsert, P., Kohler, I., Timme, S., Kiefer, S., Werner, M., Schilling, O., Vashist, Y., Makowiec, F., Brabletz, T., Hopt, U. T., Bausch, D., Kulemann, B., Keck, T., & Wellner, U. F. (2014). Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer. SURGERY, 156(1), 97-108. https://doi.org/10.1016/j.surg.2014.02.018

Vancouver

Bronsert P, Kohler I, Timme S, Kiefer S, Werner M, Schilling O et al. Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer. SURGERY. 2014 Jul;156(1):97-108. https://doi.org/10.1016/j.surg.2014.02.018

Bibtex

@article{25d17e6ea33648ffa16ab9f88f2108d9,
title = "Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer",
abstract = "BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor Zinc finger E-box binding homeobox 1 (ZEB1) in epithelial-mesenchymal transition, invasion, and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue.METHODS: Patient baseline and follow-up data were extracted from a prospectively maintained database. After clinicopathologic re-review, serial sliced tissue slides were immunostained for ZEB1, E-cadherin, vimentin, and pan-cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathologic parameters and survival after resection.RESULTS: A total of 117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer-associated fibroblasts was associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of greater than 0.10. In line with its role as an inducer of epithelial-mesenchymal transition, ZEB1 expression in cancer cells was positively correlated with Vimentin expression and negatively with E-Cadherin expression. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection.CONCLUSION: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting cancer-associated fibroblasts.",
keywords = "Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Pancreatic Ductal, Female, Fibroblasts, Homeodomain Proteins, Humans, Immunohistochemistry, Male, Middle Aged, Multivariate Analysis, Pancreatectomy, Pancreatic Neoplasms, Pancreaticoduodenectomy, Prognosis, ROC Curve, Retrospective Studies, Survival Analysis, Transcription Factors, Treatment Outcome",
author = "Peter Bronsert and Ilona Kohler and Sylvia Timme and Selina Kiefer and Martin Werner and Oliver Schilling and Yogesh Vashist and Frank Makowiec and Thomas Brabletz and Hopt, {Ulrich T} and Dirk Bausch and Birte Kulemann and Tobias Keck and Wellner, {Ulrich F}",
note = "Copyright {\textcopyright} 2014 Mosby, Inc. All rights reserved.",
year = "2014",
month = jul,
doi = "10.1016/j.surg.2014.02.018",
language = "English",
volume = "156",
pages = "97--108",
journal = "SURGERY",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer

AU - Bronsert, Peter

AU - Kohler, Ilona

AU - Timme, Sylvia

AU - Kiefer, Selina

AU - Werner, Martin

AU - Schilling, Oliver

AU - Vashist, Yogesh

AU - Makowiec, Frank

AU - Brabletz, Thomas

AU - Hopt, Ulrich T

AU - Bausch, Dirk

AU - Kulemann, Birte

AU - Keck, Tobias

AU - Wellner, Ulrich F

N1 - Copyright © 2014 Mosby, Inc. All rights reserved.

PY - 2014/7

Y1 - 2014/7

N2 - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor Zinc finger E-box binding homeobox 1 (ZEB1) in epithelial-mesenchymal transition, invasion, and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue.METHODS: Patient baseline and follow-up data were extracted from a prospectively maintained database. After clinicopathologic re-review, serial sliced tissue slides were immunostained for ZEB1, E-cadherin, vimentin, and pan-cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathologic parameters and survival after resection.RESULTS: A total of 117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer-associated fibroblasts was associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of greater than 0.10. In line with its role as an inducer of epithelial-mesenchymal transition, ZEB1 expression in cancer cells was positively correlated with Vimentin expression and negatively with E-Cadherin expression. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection.CONCLUSION: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting cancer-associated fibroblasts.

AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor Zinc finger E-box binding homeobox 1 (ZEB1) in epithelial-mesenchymal transition, invasion, and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue.METHODS: Patient baseline and follow-up data were extracted from a prospectively maintained database. After clinicopathologic re-review, serial sliced tissue slides were immunostained for ZEB1, E-cadherin, vimentin, and pan-cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathologic parameters and survival after resection.RESULTS: A total of 117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer-associated fibroblasts was associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of greater than 0.10. In line with its role as an inducer of epithelial-mesenchymal transition, ZEB1 expression in cancer cells was positively correlated with Vimentin expression and negatively with E-Cadherin expression. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection.CONCLUSION: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting cancer-associated fibroblasts.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor

KW - Carcinoma, Pancreatic Ductal

KW - Female

KW - Fibroblasts

KW - Homeodomain Proteins

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Middle Aged

KW - Multivariate Analysis

KW - Pancreatectomy

KW - Pancreatic Neoplasms

KW - Pancreaticoduodenectomy

KW - Prognosis

KW - ROC Curve

KW - Retrospective Studies

KW - Survival Analysis

KW - Transcription Factors

KW - Treatment Outcome

U2 - 10.1016/j.surg.2014.02.018

DO - 10.1016/j.surg.2014.02.018

M3 - SCORING: Journal article

C2 - 24929761

VL - 156

SP - 97

EP - 108

JO - SURGERY

JF - SURGERY

SN - 0039-6060

IS - 1

ER -