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Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma

Urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) is a heterogeneous malignancy. Through transcriptomic profiling of the Gene Expression Omnibus UBUC dataset (GSE31684), we discovered that epidermal growth factor-containing fibulin-like extracellularmatrix protein 1 (EFE...

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Autores principales: Chen, Tzu-Ju, Chan, Ti-Chun, Li, Wan-Shan, Li, Chien-Feng, Ke, Hung-Lung, Wei, Yu-Ching, Wu, Wen-Jeng, Li, Wei-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226762/
https://www.ncbi.nlm.nih.gov/pubmed/34204134
http://dx.doi.org/10.3390/genes12060872
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author Chen, Tzu-Ju
Chan, Ti-Chun
Li, Wan-Shan
Li, Chien-Feng
Ke, Hung-Lung
Wei, Yu-Ching
Wu, Wen-Jeng
Li, Wei-Ming
author_facet Chen, Tzu-Ju
Chan, Ti-Chun
Li, Wan-Shan
Li, Chien-Feng
Ke, Hung-Lung
Wei, Yu-Ching
Wu, Wen-Jeng
Li, Wei-Ming
author_sort Chen, Tzu-Ju
collection PubMed
description Urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) is a heterogeneous malignancy. Through transcriptomic profiling of the Gene Expression Omnibus UBUC dataset (GSE31684), we discovered that epidermal growth factor-containing fibulin-like extracellularmatrix protein 1 (EFEMP1) was the most upregulated gene during metastatic development. EFEMP1 is an important component of basement membranes and acts as an enzyme regulator in extracellular matrix biology. Initially, evaluation of EFEMP1 mRNA expression in 50 UBUCs showed significantly upregulated levels in high stage UC. We further validated the clinical significance of EFEMP1 in 340 UTUC and 295 UBUC using immunohistochemistry, evaluated by H-score. High EFEMP1 immunoexpression significantly correlated with high pathologic stage, high histological grade, lymph node metastasis, vascular invasion, perineural invasion and high mitosis (all p < 0.05). After adjusting for established clinicopathological factors, EFEMP1 expression status retained its prognostic impact on disease-specific survival and metastasis-free survival in UTUC and UBUC (all p < 0.01). Furthermore, Ingenuity Pathway Analysis showed that actin cytoskeleton signaling, tumor microenvironment pathway and mitochondrial dysfunction were significantly enriched by EFEMP1 dysregulation. In conclusion, high EFEMP1 expression was associated with adverse pathological features in UC and independently predicted worse outcomes, suggesting its roles in clinical decision-making and risk stratification.
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spelling pubmed-82267622021-06-26 Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma Chen, Tzu-Ju Chan, Ti-Chun Li, Wan-Shan Li, Chien-Feng Ke, Hung-Lung Wei, Yu-Ching Wu, Wen-Jeng Li, Wei-Ming Genes (Basel) Article Urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) is a heterogeneous malignancy. Through transcriptomic profiling of the Gene Expression Omnibus UBUC dataset (GSE31684), we discovered that epidermal growth factor-containing fibulin-like extracellularmatrix protein 1 (EFEMP1) was the most upregulated gene during metastatic development. EFEMP1 is an important component of basement membranes and acts as an enzyme regulator in extracellular matrix biology. Initially, evaluation of EFEMP1 mRNA expression in 50 UBUCs showed significantly upregulated levels in high stage UC. We further validated the clinical significance of EFEMP1 in 340 UTUC and 295 UBUC using immunohistochemistry, evaluated by H-score. High EFEMP1 immunoexpression significantly correlated with high pathologic stage, high histological grade, lymph node metastasis, vascular invasion, perineural invasion and high mitosis (all p < 0.05). After adjusting for established clinicopathological factors, EFEMP1 expression status retained its prognostic impact on disease-specific survival and metastasis-free survival in UTUC and UBUC (all p < 0.01). Furthermore, Ingenuity Pathway Analysis showed that actin cytoskeleton signaling, tumor microenvironment pathway and mitochondrial dysfunction were significantly enriched by EFEMP1 dysregulation. In conclusion, high EFEMP1 expression was associated with adverse pathological features in UC and independently predicted worse outcomes, suggesting its roles in clinical decision-making and risk stratification. MDPI 2021-06-06 /pmc/articles/PMC8226762/ /pubmed/34204134 http://dx.doi.org/10.3390/genes12060872 Text en © 2021 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, Tzu-Ju
Chan, Ti-Chun
Li, Wan-Shan
Li, Chien-Feng
Ke, Hung-Lung
Wei, Yu-Ching
Wu, Wen-Jeng
Li, Wei-Ming
Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma
title Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma
title_full Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma
title_fullStr Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma
title_full_unstemmed Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma
title_short Utility of EFEMP1 in the Prediction of Oncologic Outcomes of Urothelial Carcinoma
title_sort utility of efemp1 in the prediction of oncologic outcomes of urothelial carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226762/
https://www.ncbi.nlm.nih.gov/pubmed/34204134
http://dx.doi.org/10.3390/genes12060872
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