期刊论文详细信息
Cancers
Novel Genetic Variants of ALG6 and GALNTL4 of the Glycosylation Pathway Predict Cutaneous Melanoma-Specific Survival
Hongmei Nan1  Xin Li1  Sheng Luo2  Bingrong Zhou3  JeffreyE. Lee4  Qingyi Wei5  YuChen Zhao5  Hongliang Liu5  ChristopherI. Amos6 
[1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA;Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA;Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China;Department of Surgical Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA;Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA;Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX 77030, USA;
关键词: cutaneous melanoma;    expression quantitative trait loci;    glycosylation;    single-nucleotide polymorphism;    survival analysis;   
DOI  :  10.3390/cancers12020288
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

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