Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> 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...
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doaj-c4740608279c4ee180f4ec2cc743732d2020-11-25T03:32:39ZengMDPI AGCancers2072-66942020-01-0112228810.3390/cancers12020288cancers12020288Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific SurvivalBingrong Zhou0Yu Chen Zhao1Hongliang Liu2Sheng Luo3Christopher I. Amos4Jeffrey E. Lee5Xin Li6Hongmei Nan7Qingyi Wei8Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, ChinaDuke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USADuke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USADepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USAInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX 77030, USADepartment of Surgical Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USADuke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USABecause 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) (<i>ALG6</i> rs10889417 G>A and <i>GALNTL4</i> rs12270446 G>C) predicted CMSS, with an adjusted hazards ratios of 0.60 (95% confidence interval = 0.44−0.83 and <i>p</i> = 0.002) and 0.66 (0.52−0.84 and 0.004), respectively. Subsequent expression quantitative trait loci (eQTL) analysis revealed that <i>ALG6</i> rs10889417 was associated with mRNA expression levels in the cultured skin fibroblasts and whole blood cells and that <i>GALNTL4</i> rs12270446 was associated with mRNA expression levels in the skin tissues (all <i>p</i> < 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.https://www.mdpi.com/2072-6694/12/2/288cutaneous melanomaexpression quantitative trait lociglycosylationsingle-nucleotide polymorphismsurvival analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bingrong Zhou Yu Chen Zhao Hongliang Liu Sheng Luo Christopher I. Amos Jeffrey E. Lee Xin Li Hongmei Nan Qingyi Wei |
spellingShingle |
Bingrong Zhou Yu Chen Zhao Hongliang Liu Sheng Luo Christopher I. Amos Jeffrey E. Lee Xin Li Hongmei Nan Qingyi Wei Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival Cancers cutaneous melanoma expression quantitative trait loci glycosylation single-nucleotide polymorphism survival analysis |
author_facet |
Bingrong Zhou Yu Chen Zhao Hongliang Liu Sheng Luo Christopher I. Amos Jeffrey E. Lee Xin Li Hongmei Nan Qingyi Wei |
author_sort |
Bingrong Zhou |
title |
Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_short |
Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_full |
Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_fullStr |
Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_full_unstemmed |
Novel Genetic Variants of <i>ALG6</i> and <i>GALNTL4</i> of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival |
title_sort |
novel genetic variants of <i>alg6</i> and <i>galntl4</i> of the glycosylation pathway predict cutaneous melanoma-specific survival |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-01-01 |
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) (<i>ALG6</i> rs10889417 G>A and <i>GALNTL4</i> rs12270446 G>C) predicted CMSS, with an adjusted hazards ratios of 0.60 (95% confidence interval = 0.44−0.83 and <i>p</i> = 0.002) and 0.66 (0.52−0.84 and 0.004), respectively. Subsequent expression quantitative trait loci (eQTL) analysis revealed that <i>ALG6</i> rs10889417 was associated with mRNA expression levels in the cultured skin fibroblasts and whole blood cells and that <i>GALNTL4</i> rs12270446 was associated with mRNA expression levels in the skin tissues (all <i>p</i> < 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. |
topic |
cutaneous melanoma expression quantitative trait loci glycosylation single-nucleotide polymorphism survival analysis |
url |
https://www.mdpi.com/2072-6694/12/2/288 |
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