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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...

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Autores principales: Ogawa, Makiko, Tanaka, Atsushi, Namba, Kei, Shia, Jinru, Wang, Julia Y., Roehrl, Michael H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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