Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models

Background: Glycosylation changes are a main feature of cancer. Some carbohydrate epitopes and expression levels of glycosyltransferases have been used or proposed as prognostic markers, while many experimental works have investigated the role of glycosyltransferases in malignancy. Using the transcr...

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Main Authors: Michela Pucci, Martina Duca, Nadia Malagolini, Fabio Dall’Olio
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/9/2128
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author Michela Pucci
Martina Duca
Nadia Malagolini
Fabio Dall’Olio
author_facet Michela Pucci
Martina Duca
Nadia Malagolini
Fabio Dall’Olio
author_sort Michela Pucci
collection DOAJ
description Background: Glycosylation changes are a main feature of cancer. Some carbohydrate epitopes and expression levels of glycosyltransferases have been used or proposed as prognostic markers, while many experimental works have investigated the role of glycosyltransferases in malignancy. Using the transcriptomic data of the 21 TCGA cohorts, we correlated the expression level of 114 glycosyltransferases with the overall survival of patients. Methods: Using the Oncolnc website, we determined the Kaplan–Meier survival curves for the patients falling in the 15% upper or lower percentile of mRNA expression of each glycosyltransferase. Results: Seventeen glycosyltransferases involved in initial steps of N- or O-glycosylation and of glycolipid biosynthesis, in chain extension and sialylation were unequivocally associated with bad prognosis in a majority of cohorts. Four glycosyltransferases were associated with good prognosis. Other glycosyltransferases displayed an extremely high predictive value in only one or a few cohorts. The top were GALNT3, ALG6 and B3GNT7, which displayed a <i>p</i> < 1 × 10<sup>−9</sup> in the low-grade glioma (LGG) cohort. Comparison with published experimental data points to ALG3, GALNT2, B4GALNT1, POFUT1, B4GALT5, B3GNT5 and ST3GAL2 as the most consistently malignancy-associated enzymes. Conclusions: We identified several cancer-associated glycosyltransferases as potential prognostic markers and therapeutic targets.
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spelling doaj.art-33def98a46d841149c583073085a8e142023-11-23T07:55:11ZengMDPI AGCancers2072-66942022-04-01149212810.3390/cancers14092128Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental ModelsMichela Pucci0Martina Duca1Nadia Malagolini2Fabio Dall’Olio3Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Building, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyBackground: Glycosylation changes are a main feature of cancer. Some carbohydrate epitopes and expression levels of glycosyltransferases have been used or proposed as prognostic markers, while many experimental works have investigated the role of glycosyltransferases in malignancy. Using the transcriptomic data of the 21 TCGA cohorts, we correlated the expression level of 114 glycosyltransferases with the overall survival of patients. Methods: Using the Oncolnc website, we determined the Kaplan–Meier survival curves for the patients falling in the 15% upper or lower percentile of mRNA expression of each glycosyltransferase. Results: Seventeen glycosyltransferases involved in initial steps of N- or O-glycosylation and of glycolipid biosynthesis, in chain extension and sialylation were unequivocally associated with bad prognosis in a majority of cohorts. Four glycosyltransferases were associated with good prognosis. Other glycosyltransferases displayed an extremely high predictive value in only one or a few cohorts. The top were GALNT3, ALG6 and B3GNT7, which displayed a <i>p</i> < 1 × 10<sup>−9</sup> in the low-grade glioma (LGG) cohort. Comparison with published experimental data points to ALG3, GALNT2, B4GALNT1, POFUT1, B4GALT5, B3GNT5 and ST3GAL2 as the most consistently malignancy-associated enzymes. Conclusions: We identified several cancer-associated glycosyltransferases as potential prognostic markers and therapeutic targets.https://www.mdpi.com/2072-6694/14/9/2128glycosyltransferasesglycosylationKaplan–Meier survival curvesTCGAtranscriptomic analysis
spellingShingle Michela Pucci
Martina Duca
Nadia Malagolini
Fabio Dall’Olio
Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models
Cancers
glycosyltransferases
glycosylation
Kaplan–Meier survival curves
TCGA
transcriptomic analysis
title Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models
title_full Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models
title_fullStr Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models
title_full_unstemmed Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models
title_short Glycosyltransferases in Cancer: Prognostic Biomarkers of Survival in Patient Cohorts and Impact on Malignancy in Experimental Models
title_sort glycosyltransferases in cancer prognostic biomarkers of survival in patient cohorts and impact on malignancy in experimental models
topic glycosyltransferases
glycosylation
Kaplan–Meier survival curves
TCGA
transcriptomic analysis
url https://www.mdpi.com/2072-6694/14/9/2128
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AT nadiamalagolini glycosyltransferasesincancerprognosticbiomarkersofsurvivalinpatientcohortsandimpactonmalignancyinexperimentalmodels
AT fabiodallolio glycosyltransferasesincancerprognosticbiomarkersofsurvivalinpatientcohortsandimpactonmalignancyinexperimentalmodels