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GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer

GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the cli...

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Autores principales: Zhao, Zhixun, Gao, Yibo, Guan, Xu, Liu, Zheng, Jiang, Zheng, Liu, Xiuyun, Lin, Huixin, Yang, Ming, Li, Chunxiang, Yang, Runkun, Zou, Shuangmei, Wang, Xishan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071283/
https://www.ncbi.nlm.nih.gov/pubmed/30029519
http://dx.doi.org/10.3390/genes9070361
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author Zhao, Zhixun
Gao, Yibo
Guan, Xu
Liu, Zheng
Jiang, Zheng
Liu, Xiuyun
Lin, Huixin
Yang, Ming
Li, Chunxiang
Yang, Runkun
Zou, Shuangmei
Wang, Xishan
author_facet Zhao, Zhixun
Gao, Yibo
Guan, Xu
Liu, Zheng
Jiang, Zheng
Liu, Xiuyun
Lin, Huixin
Yang, Ming
Li, Chunxiang
Yang, Runkun
Zou, Shuangmei
Wang, Xishan
author_sort Zhao, Zhixun
collection PubMed
description GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B. Overexpressed GADD45B is associated with poorer prognosis for CRC patients both in overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p = 0.001) based on the TCGA database. Analysis results according to the stage II CRC cohort and the liver metastatic CRC cohort revealed that GADD45B was gradually upregulated in normal mucosa including primary colorectal cancer (PCC). Colorectal liver metastases (CLM) tissues were arranged in order (normal tissue vs. PCC p = 0.005 and PCC vs. CLM p = 0.001). The low GADD45B group had a significantly longer five-year OS (p = 0.001) and progression-free survival (PFS) (p < 0.001) than the high GADD45B group for the stage II patients. The multivariate Cox regression analysis results proved that the expression level of GADD45B was an independent prognostic factor for stage II after radical surgery (OS: Hazard Ratio (HR) 0.479, [95% confidence interval (CI) 0.305–0.753] and PFS:HR 0.490, [95% CI 0.336–0.714]). In high GADD45B expression subgroup of stage II cohort, the patients who underwent adjuvant chemotherapy had longer PFS than those who did not (p = 0.008). High expression levels of GADD45B is an independent prognostic factor of decreased OS and PFS in stage II CRC patients. The stage II CRC patients with high GADD45B expression might benefit from adjuvant chemotherapy.
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spelling pubmed-60712832018-08-09 GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer Zhao, Zhixun Gao, Yibo Guan, Xu Liu, Zheng Jiang, Zheng Liu, Xiuyun Lin, Huixin Yang, Ming Li, Chunxiang Yang, Runkun Zou, Shuangmei Wang, Xishan Genes (Basel) Article GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B. Overexpressed GADD45B is associated with poorer prognosis for CRC patients both in overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p = 0.001) based on the TCGA database. Analysis results according to the stage II CRC cohort and the liver metastatic CRC cohort revealed that GADD45B was gradually upregulated in normal mucosa including primary colorectal cancer (PCC). Colorectal liver metastases (CLM) tissues were arranged in order (normal tissue vs. PCC p = 0.005 and PCC vs. CLM p = 0.001). The low GADD45B group had a significantly longer five-year OS (p = 0.001) and progression-free survival (PFS) (p < 0.001) than the high GADD45B group for the stage II patients. The multivariate Cox regression analysis results proved that the expression level of GADD45B was an independent prognostic factor for stage II after radical surgery (OS: Hazard Ratio (HR) 0.479, [95% confidence interval (CI) 0.305–0.753] and PFS:HR 0.490, [95% CI 0.336–0.714]). In high GADD45B expression subgroup of stage II cohort, the patients who underwent adjuvant chemotherapy had longer PFS than those who did not (p = 0.008). High expression levels of GADD45B is an independent prognostic factor of decreased OS and PFS in stage II CRC patients. The stage II CRC patients with high GADD45B expression might benefit from adjuvant chemotherapy. MDPI 2018-07-19 /pmc/articles/PMC6071283/ /pubmed/30029519 http://dx.doi.org/10.3390/genes9070361 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Zhixun
Gao, Yibo
Guan, Xu
Liu, Zheng
Jiang, Zheng
Liu, Xiuyun
Lin, Huixin
Yang, Ming
Li, Chunxiang
Yang, Runkun
Zou, Shuangmei
Wang, Xishan
GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer
title GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer
title_full GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer
title_fullStr GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer
title_full_unstemmed GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer
title_short GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer
title_sort gadd45b as a prognostic and predictive biomarker in stage ii colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071283/
https://www.ncbi.nlm.nih.gov/pubmed/30029519
http://dx.doi.org/10.3390/genes9070361
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