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Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival
Because aberrant glycosylation is known to play a role in the progression of melanoma, we hypothesize that genetic variants of glycosylation pathway genes are associated with the survival of cutaneous melanoma (CM) patients. To test this hypothesis, we used a Cox proportional hazards regression mode...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072252/ https://www.ncbi.nlm.nih.gov/pubmed/31991610 http://dx.doi.org/10.3390/cancers12020288 |
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author | Zhou, Bingrong Zhao, Yu Chen Liu, Hongliang Luo, Sheng Amos, Christopher I. Lee, Jeffrey E. Li, Xin Nan, Hongmei Wei, Qingyi |
author_facet | Zhou, Bingrong Zhao, Yu Chen Liu, Hongliang Luo, Sheng Amos, Christopher I. Lee, Jeffrey E. Li, Xin Nan, Hongmei Wei, Qingyi |
author_sort | Zhou, Bingrong |
collection | PubMed |
description | Because aberrant glycosylation is known to play a role in the progression of melanoma, we hypothesize that genetic variants of glycosylation pathway genes are associated with the survival of cutaneous melanoma (CM) patients. To test this hypothesis, we used a Cox proportional hazards regression model in a single-locus analysis to evaluate associations between 34,096 genetic variants of 227 glycosylation pathway genes and CM disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from Harvard University nurse/physician cohorts. In the multivariable Cox regression analysis, we found that two novel single-nucleotide polymorphisms (SNPs) (ALG6 rs10889417 G>A and GALNTL4 rs12270446 G>C) predicted CMSS, with an adjusted hazards ratios of 0.60 (95% confidence interval = 0.44–0.83 and p = 0.002) and 0.66 (0.52–0.84 and 0.004), respectively. Subsequent expression quantitative trait loci (eQTL) analysis revealed that ALG6 rs10889417 was associated with mRNA expression levels in the cultured skin fibroblasts and whole blood cells and that GALNTL4 rs12270446 was associated with mRNA expression levels in the skin tissues (all p < 0.05). Our findings suggest that, once validated by other large patient cohorts, these two novel SNPs in the glycosylation pathway genes may be useful prognostic biomarkers for CMSS, likely through modulating their gene expression. |
format | Online Article Text |
id | pubmed-7072252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70722522020-03-19 Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival Zhou, Bingrong Zhao, Yu Chen Liu, Hongliang Luo, Sheng Amos, Christopher I. Lee, Jeffrey E. Li, Xin Nan, Hongmei Wei, Qingyi Cancers (Basel) Article Because aberrant glycosylation is known to play a role in the progression of melanoma, we hypothesize that genetic variants of glycosylation pathway genes are associated with the survival of cutaneous melanoma (CM) patients. To test this hypothesis, we used a Cox proportional hazards regression model in a single-locus analysis to evaluate associations between 34,096 genetic variants of 227 glycosylation pathway genes and CM disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from Harvard University nurse/physician cohorts. In the multivariable Cox regression analysis, we found that two novel single-nucleotide polymorphisms (SNPs) (ALG6 rs10889417 G>A and GALNTL4 rs12270446 G>C) predicted CMSS, with an adjusted hazards ratios of 0.60 (95% confidence interval = 0.44–0.83 and p = 0.002) and 0.66 (0.52–0.84 and 0.004), respectively. Subsequent expression quantitative trait loci (eQTL) analysis revealed that ALG6 rs10889417 was associated with mRNA expression levels in the cultured skin fibroblasts and whole blood cells and that GALNTL4 rs12270446 was associated with mRNA expression levels in the skin tissues (all p < 0.05). Our findings suggest that, once validated by other large patient cohorts, these two novel SNPs in the glycosylation pathway genes may be useful prognostic biomarkers for CMSS, likely through modulating their gene expression. MDPI 2020-01-24 /pmc/articles/PMC7072252/ /pubmed/31991610 http://dx.doi.org/10.3390/cancers12020288 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhou, Bingrong Zhao, Yu Chen Liu, Hongliang Luo, Sheng Amos, Christopher I. Lee, Jeffrey E. Li, Xin Nan, Hongmei Wei, Qingyi Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title | Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_full | Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_fullStr | Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_full_unstemmed | Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_short | Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_sort | novel genetic variants of alg6 and galntl4 of the glycosylation pathway predict cutaneous melanoma-specific survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072252/ https://www.ncbi.nlm.nih.gov/pubmed/31991610 http://dx.doi.org/10.3390/cancers12020288 |
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