Early-stage loss of GALNT6 predicts poor clinical outcome in colorectal cancer Journal Article
| Authors: | Ogawa, M.; Tanaka, A.; Namba, K.; Shia, J.; Wang, J. Y.; Roehrl, M. H. |
| Article Title: | Early-stage loss of GALNT6 predicts poor clinical outcome in colorectal cancer |
| Abstract: | 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. Copyright © 2022 Ogawa, Tanaka, Namba, Shia, Wang and Roehrl. |
| Keywords: | immunohistochemistry; cancer survival; human tissue; protein expression; aged; unclassified drug; gene mutation; major clinical study; overall survival; cancer growth; disease free survival; cancer staging; outcome assessment; colorectal cancer; gene expression; tumor differentiation; histology; microsatellite instability; glycosylation; cancer tissue; tissue microarray; k ras protein; b raf kinase; perineural invasion; mucin; clinical outcome; early stage; risk prediction; lymph vessel metastasis; human; male; female; article; n acetylgalactosaminyltransferase; galnt6; polypeptide n acteylgalactosaminyltransferase 6 |
| Journal Title: | Frontiers in Oncology |
| Volume: | 12 |
| ISSN: | 2234-943X |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2022-05-01 |
| Start Page: | 802548 |
| Language: | English |
| DOI: | 10.3389/fonc.2022.802548 |
| PROVIDER: | scopus |
| PMCID: | PMC9185839 |
| PUBMED: | 35692787 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
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