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Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma

BACKGROUND: GATA binding protein 3 (GATA3) was recently proposed to function as a tumor suppressor gene in some types of human cancer. This study aims to investigate GATA3 expression and its prognostic significance in primary gastric adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time qu...

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Autores principales: Keshari, Rajiv Prasad, Wang, Wei, Zhang, Yu, Wang, Dan-dan, Li, Yuan-fang, Yuan, Shu-qiang, Qiu, Hai-bo, Huang, Chun-yu, Chen, Yong-ming, Xia, Jian-chuan, Zhou, Zhi-wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913598/
https://www.ncbi.nlm.nih.gov/pubmed/24504018
http://dx.doi.org/10.1371/journal.pone.0087195
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author Keshari, Rajiv Prasad
Wang, Wei
Zhang, Yu
Wang, Dan-dan
Li, Yuan-fang
Yuan, Shu-qiang
Qiu, Hai-bo
Huang, Chun-yu
Chen, Yong-ming
Xia, Jian-chuan
Zhou, Zhi-wei
author_facet Keshari, Rajiv Prasad
Wang, Wei
Zhang, Yu
Wang, Dan-dan
Li, Yuan-fang
Yuan, Shu-qiang
Qiu, Hai-bo
Huang, Chun-yu
Chen, Yong-ming
Xia, Jian-chuan
Zhou, Zhi-wei
author_sort Keshari, Rajiv Prasad
collection PubMed
description BACKGROUND: GATA binding protein 3 (GATA3) was recently proposed to function as a tumor suppressor gene in some types of human cancer. This study aims to investigate GATA3 expression and its prognostic significance in primary gastric adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time quantitative PCR (RT-qPCR) and immunohistochemical staining methods, GATA3 expression was analyzed in tissue samples from a consecutive series of 402 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between GATA3 expression, clinicopathological factors, and patient survival was investigated. The expression status of GATA3 was shown to be clearly reduced in the tumor tissue samples compared with that in the matched adjacent non-tumor tissue samples by RT-qPCR (P = 0.0014). Immunohistochemistry analysis indicated that GATA3 expression was significantly decreased in 225 of the 402 (56%) gastric adenocarcinoma cases. Reduced GATA3 expression was also observed in patients with large tumors (P = 0.017), signet ring cell carcinoma or mucinous carcinoma (P = 0.005) and tumors with lymphatic or venous invasion (P = 0.040). Additionally, reduced expression of GATA3 was more commonly observed in tumors that were staged as T4a/b (P<0.001), N3 (P<0.001), or M1 (P<0.001). Kaplan-Meier survival curves revealed that reduced expression of GATA3 was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001). Multivariate Cox analysis identified GATA3 expression as an independent prognostic factor for overall survival (HR = 5.375, 95% CI = 3.647–7.921, P<0.001). To investigate the predictive ability of the models with and without containing GATA3 gene expression, Harrell's c-index was calculated as a measure of predictive accuracy of survival outcome. The c-index values revealed that model containing GATA3 expression (c-index = 0.897) had superior discrimination ability to the model without containg it (c-index = 0.811). CONCLUSIONS/SIGNIFICANCE: Our data suggest that GATA3 plays an important role in tumor progression and that reduced GATA3 expression independently predicts an unfavorable prognosis in primary gastric adenocarcinoma patients.
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spelling pubmed-39135982014-02-06 Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma Keshari, Rajiv Prasad Wang, Wei Zhang, Yu Wang, Dan-dan Li, Yuan-fang Yuan, Shu-qiang Qiu, Hai-bo Huang, Chun-yu Chen, Yong-ming Xia, Jian-chuan Zhou, Zhi-wei PLoS One Research Article BACKGROUND: GATA binding protein 3 (GATA3) was recently proposed to function as a tumor suppressor gene in some types of human cancer. This study aims to investigate GATA3 expression and its prognostic significance in primary gastric adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time quantitative PCR (RT-qPCR) and immunohistochemical staining methods, GATA3 expression was analyzed in tissue samples from a consecutive series of 402 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between GATA3 expression, clinicopathological factors, and patient survival was investigated. The expression status of GATA3 was shown to be clearly reduced in the tumor tissue samples compared with that in the matched adjacent non-tumor tissue samples by RT-qPCR (P = 0.0014). Immunohistochemistry analysis indicated that GATA3 expression was significantly decreased in 225 of the 402 (56%) gastric adenocarcinoma cases. Reduced GATA3 expression was also observed in patients with large tumors (P = 0.017), signet ring cell carcinoma or mucinous carcinoma (P = 0.005) and tumors with lymphatic or venous invasion (P = 0.040). Additionally, reduced expression of GATA3 was more commonly observed in tumors that were staged as T4a/b (P<0.001), N3 (P<0.001), or M1 (P<0.001). Kaplan-Meier survival curves revealed that reduced expression of GATA3 was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001). Multivariate Cox analysis identified GATA3 expression as an independent prognostic factor for overall survival (HR = 5.375, 95% CI = 3.647–7.921, P<0.001). To investigate the predictive ability of the models with and without containing GATA3 gene expression, Harrell's c-index was calculated as a measure of predictive accuracy of survival outcome. The c-index values revealed that model containing GATA3 expression (c-index = 0.897) had superior discrimination ability to the model without containg it (c-index = 0.811). CONCLUSIONS/SIGNIFICANCE: Our data suggest that GATA3 plays an important role in tumor progression and that reduced GATA3 expression independently predicts an unfavorable prognosis in primary gastric adenocarcinoma patients. Public Library of Science 2014-02-04 /pmc/articles/PMC3913598/ /pubmed/24504018 http://dx.doi.org/10.1371/journal.pone.0087195 Text en © 2014 Keshari 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
Keshari, Rajiv Prasad
Wang, Wei
Zhang, Yu
Wang, Dan-dan
Li, Yuan-fang
Yuan, Shu-qiang
Qiu, Hai-bo
Huang, Chun-yu
Chen, Yong-ming
Xia, Jian-chuan
Zhou, Zhi-wei
Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma
title Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma
title_full Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma
title_fullStr Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma
title_full_unstemmed Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma
title_short Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma
title_sort decreased expression of the gata3 gene is associated with poor prognosis in primary gastric adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913598/
https://www.ncbi.nlm.nih.gov/pubmed/24504018
http://dx.doi.org/10.1371/journal.pone.0087195
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