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Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer
BACKGROUND: The B3GNT6 protein is a member of the O-GlcNAc transferase (OGT) family and is responsible for the production of the core 3 structure of O-glycans. It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexpl...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988341/ https://www.ncbi.nlm.nih.gov/pubmed/35387659 http://dx.doi.org/10.1186/s12957-022-02561-x |
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author | Xiao, Shihan Yang, Chen Zhang, Yang Lai, Chen |
author_facet | Xiao, Shihan Yang, Chen Zhang, Yang Lai, Chen |
author_sort | Xiao, Shihan |
collection | PubMed |
description | BACKGROUND: The B3GNT6 protein is a member of the O-GlcNAc transferase (OGT) family and is responsible for the production of the core 3 structure of O-glycans. It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexplored. METHODS: We obtained mRNA transcriptomic sequencing data from 3 gene expression omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer. We further validated this at the protein level in our cohort using immunohistochemical staining of B3GNT6 as well as the Human Protein Atlas online database. RESULTS: B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels. Downregulation of B3GNT6 expression was found to be associated with poor overall survival in patients with colorectal cancer as per the data in GSE39582 and TCGA databases. Low B3GNT6 mRNA levels were significantly associated with chromosome instability (CIN) and KRAS mutations in patients with colorectal cancer. Gene set enrichment analysis (GSEA) revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity. CONCLUSIONS: The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC. Moreover, the low expression of B3GNT6 may indicate more frequent activation of the KRAS/ERK signaling pathway, high CIN, and increased proteasomal activity. These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-022-02561-x. |
format | Online Article Text |
id | pubmed-8988341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89883412022-04-08 Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer Xiao, Shihan Yang, Chen Zhang, Yang Lai, Chen World J Surg Oncol Research BACKGROUND: The B3GNT6 protein is a member of the O-GlcNAc transferase (OGT) family and is responsible for the production of the core 3 structure of O-glycans. It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexplored. METHODS: We obtained mRNA transcriptomic sequencing data from 3 gene expression omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer. We further validated this at the protein level in our cohort using immunohistochemical staining of B3GNT6 as well as the Human Protein Atlas online database. RESULTS: B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels. Downregulation of B3GNT6 expression was found to be associated with poor overall survival in patients with colorectal cancer as per the data in GSE39582 and TCGA databases. Low B3GNT6 mRNA levels were significantly associated with chromosome instability (CIN) and KRAS mutations in patients with colorectal cancer. Gene set enrichment analysis (GSEA) revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity. CONCLUSIONS: The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC. Moreover, the low expression of B3GNT6 may indicate more frequent activation of the KRAS/ERK signaling pathway, high CIN, and increased proteasomal activity. These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-022-02561-x. BioMed Central 2022-04-07 /pmc/articles/PMC8988341/ /pubmed/35387659 http://dx.doi.org/10.1186/s12957-022-02561-x Text en © The Author(s) 2022 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 | Research Xiao, Shihan Yang, Chen Zhang, Yang Lai, Chen Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer |
title | Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer |
title_full | Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer |
title_fullStr | Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer |
title_full_unstemmed | Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer |
title_short | Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer |
title_sort | downregulation of b3gnt6 is a predictor of poor outcomes in patients with colorectal cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988341/ https://www.ncbi.nlm.nih.gov/pubmed/35387659 http://dx.doi.org/10.1186/s12957-022-02561-x |
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