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High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer

BACKGROUND: Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of...

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Autores principales: Zhao, Zongxian, Li, Shuliang, Li, Shilong, Wang, Jun, Lin, Hai, Fu, Weihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447617/
https://www.ncbi.nlm.nih.gov/pubmed/34530820
http://dx.doi.org/10.1186/s12935-021-02071-y
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author Zhao, Zongxian
Li, Shuliang
Li, Shilong
Wang, Jun
Lin, Hai
Fu, Weihua
author_facet Zhao, Zongxian
Li, Shuliang
Li, Shilong
Wang, Jun
Lin, Hai
Fu, Weihua
author_sort Zhao, Zongxian
collection PubMed
description BACKGROUND: Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. METHODS: The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. RESULTS: CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). CONCLUSION: CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02071-y.
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spelling pubmed-84476172021-09-17 High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer Zhao, Zongxian Li, Shuliang Li, Shilong Wang, Jun Lin, Hai Fu, Weihua Cancer Cell Int Primary Research BACKGROUND: Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. METHODS: The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. RESULTS: CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). CONCLUSION: CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02071-y. BioMed Central 2021-09-16 /pmc/articles/PMC8447617/ /pubmed/34530820 http://dx.doi.org/10.1186/s12935-021-02071-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Zhao, Zongxian
Li, Shuliang
Li, Shilong
Wang, Jun
Lin, Hai
Fu, Weihua
High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
title High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
title_full High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
title_fullStr High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
title_full_unstemmed High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
title_short High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
title_sort high expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447617/
https://www.ncbi.nlm.nih.gov/pubmed/34530820
http://dx.doi.org/10.1186/s12935-021-02071-y
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