Cargando…

Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling

SIMPLE SUMMARY: This research leveraged three-dimensional confocal imaging to examine elafin’s spatial distribution in locoregional esophageal squamous cell carcinoma (ESCC) tumors. Our findings highlighted distinct elafin localizations in patients with poor versus favorable prognoses. Elafin expres...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Wei-Chung, Wu, Chun-Chieh, Liu, Yu-Peng, Zhuo, Guan-Yu, Wang, Yao-Kuang, Chen, Yi-Hsun, Chen, Chu-Chih, Wang, Yin-Han, Wu, Ming-Tsang, Wu, I-Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417143/
https://www.ncbi.nlm.nih.gov/pubmed/37568641
http://dx.doi.org/10.3390/cancers15153825
_version_ 1785087953189470208
author Chen, Wei-Chung
Wu, Chun-Chieh
Liu, Yu-Peng
Zhuo, Guan-Yu
Wang, Yao-Kuang
Chen, Yi-Hsun
Chen, Chu-Chih
Wang, Yin-Han
Wu, Ming-Tsang
Wu, I-Chen
author_facet Chen, Wei-Chung
Wu, Chun-Chieh
Liu, Yu-Peng
Zhuo, Guan-Yu
Wang, Yao-Kuang
Chen, Yi-Hsun
Chen, Chu-Chih
Wang, Yin-Han
Wu, Ming-Tsang
Wu, I-Chen
author_sort Chen, Wei-Chung
collection PubMed
description SIMPLE SUMMARY: This research leveraged three-dimensional confocal imaging to examine elafin’s spatial distribution in locoregional esophageal squamous cell carcinoma (ESCC) tumors. Our findings highlighted distinct elafin localizations in patients with poor versus favorable prognoses. Elafin expression was significantly higher in tumor regions, contributing to a poorer prognosis. Complementary in vitro studies revealed that elafin promotes ESCC cell proliferation, migration, and invasion via the epithelial–mesenchymal transition pathway. These findings suggest that the targeted inhibition of elafin could potentially serve as a novel therapeutic approach aimed at improving survival rates in patients with locoregional ESCC. ABSTRACT: Esophageal cancers are globally the sixth deadliest malignancy, with limited curative options. The association of high serum elafin levels, a molecule produced by epithelial cells, with esophageal squamous cell carcinoma (ESCC) risk is established, but its link to poor ESCC prognosis remains unclear. To explore this question, we first used three-dimensional confocal imaging to create a model of the spatial distribution of elafin inside locoregional ESCC tissues. Then, after analyzing data obtained from whole-genome microarrays for ESCC cell lines and their more invasive sublines, we performed in vitro experiments using RNA sequencing to identify possible elafin-related pathways. Three-dimensional tissue imaging showed elafin distributed as an interweaved-like fibrous structure in the stroma of tissue obtained from patients with high serum levels of elafin and poorer prognoses. By contrast, the signal was confined inside or around the tumor nest in patients who had lower serum levels and better survival. The analysis of a TCGA dataset revealed that higher levels of elafin mRNA in stage I–IIIA ESCC patients were associated with shorter survival. The in vitro studies revealed that elafin promoted ESCC cell proliferation, migration, and invasion via the epithelial–mesenchymal transition pathway. Thus, elafin inhibition could potentially be used therapeutically to improve survival in patients with locoregional ESCC.
format Online
Article
Text
id pubmed-10417143
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-104171432023-08-12 Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling Chen, Wei-Chung Wu, Chun-Chieh Liu, Yu-Peng Zhuo, Guan-Yu Wang, Yao-Kuang Chen, Yi-Hsun Chen, Chu-Chih Wang, Yin-Han Wu, Ming-Tsang Wu, I-Chen Cancers (Basel) Article SIMPLE SUMMARY: This research leveraged three-dimensional confocal imaging to examine elafin’s spatial distribution in locoregional esophageal squamous cell carcinoma (ESCC) tumors. Our findings highlighted distinct elafin localizations in patients with poor versus favorable prognoses. Elafin expression was significantly higher in tumor regions, contributing to a poorer prognosis. Complementary in vitro studies revealed that elafin promotes ESCC cell proliferation, migration, and invasion via the epithelial–mesenchymal transition pathway. These findings suggest that the targeted inhibition of elafin could potentially serve as a novel therapeutic approach aimed at improving survival rates in patients with locoregional ESCC. ABSTRACT: Esophageal cancers are globally the sixth deadliest malignancy, with limited curative options. The association of high serum elafin levels, a molecule produced by epithelial cells, with esophageal squamous cell carcinoma (ESCC) risk is established, but its link to poor ESCC prognosis remains unclear. To explore this question, we first used three-dimensional confocal imaging to create a model of the spatial distribution of elafin inside locoregional ESCC tissues. Then, after analyzing data obtained from whole-genome microarrays for ESCC cell lines and their more invasive sublines, we performed in vitro experiments using RNA sequencing to identify possible elafin-related pathways. Three-dimensional tissue imaging showed elafin distributed as an interweaved-like fibrous structure in the stroma of tissue obtained from patients with high serum levels of elafin and poorer prognoses. By contrast, the signal was confined inside or around the tumor nest in patients who had lower serum levels and better survival. The analysis of a TCGA dataset revealed that higher levels of elafin mRNA in stage I–IIIA ESCC patients were associated with shorter survival. The in vitro studies revealed that elafin promoted ESCC cell proliferation, migration, and invasion via the epithelial–mesenchymal transition pathway. Thus, elafin inhibition could potentially be used therapeutically to improve survival in patients with locoregional ESCC. MDPI 2023-07-27 /pmc/articles/PMC10417143/ /pubmed/37568641 http://dx.doi.org/10.3390/cancers15153825 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Wei-Chung
Wu, Chun-Chieh
Liu, Yu-Peng
Zhuo, Guan-Yu
Wang, Yao-Kuang
Chen, Yi-Hsun
Chen, Chu-Chih
Wang, Yin-Han
Wu, Ming-Tsang
Wu, I-Chen
Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling
title Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling
title_full Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling
title_fullStr Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling
title_full_unstemmed Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling
title_short Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study Using Three-Dimensional Imaging and Genomic Profiling
title_sort elafin as a prognostic marker in esophageal squamous cell carcinoma: a pilot study using three-dimensional imaging and genomic profiling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417143/
https://www.ncbi.nlm.nih.gov/pubmed/37568641
http://dx.doi.org/10.3390/cancers15153825
work_keys_str_mv AT chenweichung elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT wuchunchieh elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT liuyupeng elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT zhuoguanyu elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT wangyaokuang elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT chenyihsun elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT chenchuchih elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT wangyinhan elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT wumingtsang elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling
AT wuichen elafinasaprognosticmarkerinesophagealsquamouscellcarcinomaapilotstudyusingthreedimensionalimagingandgenomicprofiling