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PMID: 24945657 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma.

PloS one ·Vol. 9 ·No. 6 ·2014-00-00 ·Pages e99955

Ha SY, Yeo SY, Xuan YH, Kim SH

Abstract

Cancer-associated fibroblasts (CAF) are activated fibroblasts in the cancer stroma and play an important role in cancer progression. Some reports have indicated the correlation between the expression of CAF markers and adverse prognosis in several cancers. However, no reports have studied CAF phenotype and its clinical relevance in esophageal squamous cell carcinoma (ESCC). We investigated CAF phenotype of ESCC based on histology and immunohistochemical expressions of five CAF markers such as fibroblast activation protein (FAP), smooth muscle actin (SMA), fibroblast-specific protein-1 (FSP1), platelet-derived growth factor receptor (PDGFRα), and PDGFRβ in 116 ESCC tissue samples. Besides, we also examined the correlation of the CAF phenotype with clinical relevance as well as other cancer-microenvironment related factors. Histologically immature CAF phenotype was correlated with poor prognosis (p<0.001) and associated with increased microvessel density, increased tumor associated macrophages, and epithelial to mesenchymal transition. CAF markers were characteristically expressed in stromal fibroblast close to tumor cells and the expression pattern of 5 CAF markers was highly heterogeneous in every individual cases. Of five CAF markers, SMA, FSP1, and PDGFRα were unfavorable prognostic indicators of ESCC. The number of positive CAF markers was greater in ESCC with immature CAFs than in those with mature ones. Our results demonstrate that histologic classification of CAF phenotype is a reliable and significant prognostic predictor in ESCC. CAF markers have the potential to be diagnostic and therapeutic targets in ESCC.

MeSH Terms
Actins/genetics,metabolism Aged Biomarkers, Tumor/genetics,metabolism Calcium-Binding Proteins/genetics,metabolism Carcinoma, Squamous Cell/genetics,metabolism,mortality,pathology Endopeptidases Epithelial-Mesenchymal Transition/genetics Esophageal Neoplasms/genetics,metabolism,mortality,pathology Esophageal Squamous Cell Carcinoma Female Fibroblasts/metabolism,pathology Gelatinases/genetics,metabolism Gene Expression Humans Macrophages/metabolism,pathology Male Membrane Proteins/genetics,metabolism Middle Aged Phenotype Prognosis Receptor, Platelet-Derived Growth Factor alpha/genetics,metabolism Receptor, Platelet-Derived Growth Factor beta/genetics,metabolism S100 Calcium-Binding Protein A4 Serine Endopeptidases/genetics,metabolism Survival Analysis Tissue Array Analysis Tumor Microenvironment/genetics
Chemicals
ACTA2 protein, human Actins Biomarkers, Tumor Calcium-Binding Proteins Membrane Proteins S100 Calcium-Binding Protein A4 S100A4 protein, human Receptor, Platelet-Derived Growth Factor alpha Receptor, Platelet-Derived Growth Factor beta Endopeptidases Serine Endopeptidases fibroblast activation protein alpha Gelatinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ha Sang Yun
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yeo So-Young
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
Xuan Yan-hiua
Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji, China; Department of Pathology, Yanbian University School of Medicine, Yanji, China.
Kim Seok-Hyung
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0099955
Published
2014-00-00
Epub
2014-00-19
Pages
e99955
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC4063790
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0099955 PMC Full Text View journal details
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