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Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma
AIMS: The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and pro...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990633/ https://www.ncbi.nlm.nih.gov/pubmed/24743601 http://dx.doi.org/10.1371/journal.pone.0095386 |
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author | Qi, Yi-Jun Wang, Ming Liu, Rui-Min Wei, Hua Chao, Wei-Xia Zhang, Tian Lou, Qiang Li, Xiu-Min Ma, Jin Zhu, Han Yang, Zhen-Hua Liu, Hai-Qing Ma, Yuan-Fang |
author_facet | Qi, Yi-Jun Wang, Ming Liu, Rui-Min Wei, Hua Chao, Wei-Xia Zhang, Tian Lou, Qiang Li, Xiu-Min Ma, Jin Zhu, Han Yang, Zhen-Hua Liu, Hai-Qing Ma, Yuan-Fang |
author_sort | Qi, Yi-Jun |
collection | PubMed |
description | AIMS: The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis. MATERIALS AND METHODS: Western blot was used to examine 14-3-3σ protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to IV stage and various esophageal epithelial cell lines with different biological behavior. Immunohistochemistry was used to estimate 14-3-3σ protein in 110 biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had follow-up data. Support vector machine (SVM) was used to develop a classifier for prognosis. RESULTS: 14-3-3σ decreased progressively from NEE to LGIN, to HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed high expression of 14-3-3σ protein compared with non-chemoresistant ESCC cell lines and immortalized NEC. Furthermore, the downregulation of 14-3-3σ correlated significantly with histological grade (P = 0.000) and worse prognosis (P = 0.004). Multivariate Cox regression analysis indicated that 14-3-3σ protein (P = 0.016) and T stage (P = 0.000) were independent prognostic factors for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological grade, lymph node metastasis, clinical stage and 14-3-3σ, distinguished significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P = 0.000). CONCLUSIONS: Downregulation of 14-3-3σ arises early in the development of ESCC and predicts poor survival, suggesting that 14-3-3σ may be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. Our seven-feature SVM classifier for ESCC prognosis may help to inform clinical decisions and tailor individual therapy. |
format | Online Article Text |
id | pubmed-3990633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39906332014-04-21 Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma Qi, Yi-Jun Wang, Ming Liu, Rui-Min Wei, Hua Chao, Wei-Xia Zhang, Tian Lou, Qiang Li, Xiu-Min Ma, Jin Zhu, Han Yang, Zhen-Hua Liu, Hai-Qing Ma, Yuan-Fang PLoS One Research Article AIMS: The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis. MATERIALS AND METHODS: Western blot was used to examine 14-3-3σ protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to IV stage and various esophageal epithelial cell lines with different biological behavior. Immunohistochemistry was used to estimate 14-3-3σ protein in 110 biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had follow-up data. Support vector machine (SVM) was used to develop a classifier for prognosis. RESULTS: 14-3-3σ decreased progressively from NEE to LGIN, to HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed high expression of 14-3-3σ protein compared with non-chemoresistant ESCC cell lines and immortalized NEC. Furthermore, the downregulation of 14-3-3σ correlated significantly with histological grade (P = 0.000) and worse prognosis (P = 0.004). Multivariate Cox regression analysis indicated that 14-3-3σ protein (P = 0.016) and T stage (P = 0.000) were independent prognostic factors for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological grade, lymph node metastasis, clinical stage and 14-3-3σ, distinguished significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P = 0.000). CONCLUSIONS: Downregulation of 14-3-3σ arises early in the development of ESCC and predicts poor survival, suggesting that 14-3-3σ may be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. Our seven-feature SVM classifier for ESCC prognosis may help to inform clinical decisions and tailor individual therapy. Public Library of Science 2014-04-17 /pmc/articles/PMC3990633/ /pubmed/24743601 http://dx.doi.org/10.1371/journal.pone.0095386 Text en © 2014 Qi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Qi, Yi-Jun Wang, Ming Liu, Rui-Min Wei, Hua Chao, Wei-Xia Zhang, Tian Lou, Qiang Li, Xiu-Min Ma, Jin Zhu, Han Yang, Zhen-Hua Liu, Hai-Qing Ma, Yuan-Fang Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma |
title | Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma |
title_full | Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma |
title_fullStr | Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma |
title_full_unstemmed | Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma |
title_short | Downregulation of 14-3-3σ Correlates with Multistage Carcinogenesis and Poor Prognosis of Esophageal Squamous Cell Carcinoma |
title_sort | downregulation of 14-3-3σ correlates with multistage carcinogenesis and poor prognosis of esophageal squamous cell carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990633/ https://www.ncbi.nlm.nih.gov/pubmed/24743601 http://dx.doi.org/10.1371/journal.pone.0095386 |
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