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Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer
Colorectal adenocarcinomas arise from luminal lining epithelium of the colorectal tract which is covered with highly glycosylated mucins. Mucin O-glycosylation is initiated by a family of polypeptide N-acteylgalactosaminyltransferases (GALNTs). This study examined GALNT6 protein expression in 679 co...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185839/ https://www.ncbi.nlm.nih.gov/pubmed/35692787 http://dx.doi.org/10.3389/fonc.2022.802548 |
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author | Ogawa, Makiko Tanaka, Atsushi Namba, Kei Shia, Jinru Wang, Julia Y. Roehrl, Michael H. |
author_facet | Ogawa, Makiko Tanaka, Atsushi Namba, Kei Shia, Jinru Wang, Julia Y. Roehrl, Michael H. |
author_sort | Ogawa, Makiko |
collection | PubMed |
description | Colorectal adenocarcinomas arise from luminal lining epithelium of the colorectal tract which is covered with highly glycosylated mucins. Mucin O-glycosylation is initiated by a family of polypeptide N-acteylgalactosaminyltransferases (GALNTs). This study examined GALNT6 protein expression in 679 colorectal tumors, including 574 early-stage and 105 late-stage cancers. GALNT6 expression in cancer tissue varied widely between patients ranging from high levels to complete loss. Loss of GALNT6 occurred in 9.9% of early-stage and 15.2% of late-stage cancers and was more prevalent in grade 3 or MSI subtype tumors. Survival analyses revealed that loss of GALNT6 expression is prognostic of reduced overall survival, and univariate and multivariate analyses demonstrated that loss of GALNT6 is an independent risk variable. We also analyzed 508-case TCGA and 63-case CPTAC colorectal cancer cohorts for all members of the GALNT enzyme family, the mucin family, as well as KRAS and BRAF mutations. GLANT6 mRNA expression showed no strong correlation with other GALNTs or mucins but was significantly higher in KRAS mutated or BRAF wild-type early-stage cancers. Using large cohorts of patients and different approaches, this study shows that loss of GALNT6 enzyme in early-stage colorectal cancer predicts poor clinical outcomes. |
format | Online Article Text |
id | pubmed-9185839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91858392022-06-11 Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer Ogawa, Makiko Tanaka, Atsushi Namba, Kei Shia, Jinru Wang, Julia Y. Roehrl, Michael H. Front Oncol Oncology Colorectal adenocarcinomas arise from luminal lining epithelium of the colorectal tract which is covered with highly glycosylated mucins. Mucin O-glycosylation is initiated by a family of polypeptide N-acteylgalactosaminyltransferases (GALNTs). This study examined GALNT6 protein expression in 679 colorectal tumors, including 574 early-stage and 105 late-stage cancers. GALNT6 expression in cancer tissue varied widely between patients ranging from high levels to complete loss. Loss of GALNT6 occurred in 9.9% of early-stage and 15.2% of late-stage cancers and was more prevalent in grade 3 or MSI subtype tumors. Survival analyses revealed that loss of GALNT6 expression is prognostic of reduced overall survival, and univariate and multivariate analyses demonstrated that loss of GALNT6 is an independent risk variable. We also analyzed 508-case TCGA and 63-case CPTAC colorectal cancer cohorts for all members of the GALNT enzyme family, the mucin family, as well as KRAS and BRAF mutations. GLANT6 mRNA expression showed no strong correlation with other GALNTs or mucins but was significantly higher in KRAS mutated or BRAF wild-type early-stage cancers. Using large cohorts of patients and different approaches, this study shows that loss of GALNT6 enzyme in early-stage colorectal cancer predicts poor clinical outcomes. Frontiers Media S.A. 2022-05-27 /pmc/articles/PMC9185839/ /pubmed/35692787 http://dx.doi.org/10.3389/fonc.2022.802548 Text en Copyright © 2022 Ogawa, Tanaka, Namba, Shia, Wang and Roehrl https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ogawa, Makiko Tanaka, Atsushi Namba, Kei Shia, Jinru Wang, Julia Y. Roehrl, Michael H. Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer |
title | Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer |
title_full | Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer |
title_fullStr | Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer |
title_full_unstemmed | Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer |
title_short | Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer |
title_sort | early-stage loss of galnt6 predicts poor clinical outcome in colorectal cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185839/ https://www.ncbi.nlm.nih.gov/pubmed/35692787 http://dx.doi.org/10.3389/fonc.2022.802548 |
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