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Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival.

Publication ,  Journal Article
Zhou, B; Zhao, YC; Liu, H; Luo, S; Amos, CI; Lee, JE; Li, X; Nan, H; Wei, Q
Published in: Cancers (Basel)
January 24, 2020

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.

Duke Scholars

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Published In

Cancers (Basel)

DOI

ISSN

2072-6694

Publication Date

January 24, 2020

Volume

12

Issue

2

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

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Zhou, B., Zhao, Y. C., Liu, H., Luo, S., Amos, C. I., Lee, J. E., … Wei, Q. (2020). Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival. Cancers (Basel), 12(2). https://doi.org/10.3390/cancers12020288
Zhou, Bingrong, Yu Chen Zhao, Hongliang Liu, Sheng Luo, Christopher I. Amos, Jeffrey E. Lee, Xin Li, Hongmei Nan, and Qingyi Wei. “Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival.Cancers (Basel) 12, no. 2 (January 24, 2020). https://doi.org/10.3390/cancers12020288.
Zhou B, Zhao YC, Liu H, Luo S, Amos CI, Lee JE, et al. Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival. Cancers (Basel). 2020 Jan 24;12(2).
Zhou, Bingrong, et al. “Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival.Cancers (Basel), vol. 12, no. 2, Jan. 2020. Pubmed, doi:10.3390/cancers12020288.
Zhou B, Zhao YC, Liu H, Luo S, Amos CI, Lee JE, Li X, Nan H, Wei Q. Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival. Cancers (Basel). 2020 Jan 24;12(2).

Published In

Cancers (Basel)

DOI

ISSN

2072-6694

Publication Date

January 24, 2020

Volume

12

Issue

2

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis