Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma.

dc.contributor.author

Zhang, Weikang

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Liu, Hongliang

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Liu, Zhensheng

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Zhu, Dakai

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Amos, Christopher I

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Fang, Shenying

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Lee, Jeffrey E

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Wei, Qingyi

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United States

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2015-10-07T16:12:01Z

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2015-07

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BACKGROUND: The Notch signaling pathway is constitutively activated in human cutaneous melanoma to promote growth and aggressive metastatic potential of primary melanoma cells. Therefore, genetic variants in Notch pathway genes may affect the prognosis of cutaneous melanoma patients. METHODS: We identified 6,256 SNPs in 48 Notch genes in 858 cutaneous melanoma patients included in a previously published cutaneous melanoma genome-wide association study dataset. Multivariate and stepwise Cox proportional hazards regression and false-positive report probability corrections were performed to evaluate associations between putative functional SNPs and cutaneous melanoma disease-specific survival. Receiver operating characteristic curve was constructed, and area under the curve was used to assess the classification performance of the model. RESULTS: Four putative functional SNPs of Notch pathway genes had independent and joint predictive roles in survival of cutaneous melanoma patients. The most significant variant was NCOR2 rs2342924 T>C (adjusted HR, 2.71; 95% confidence interval, 1.73-4.23; Ptrend = 9.62 × 10(-7)), followed by NCSTN rs1124379 G>A, NCOR2 rs10846684 G>A, and MAML2 rs7953425 G>A (Ptrend = 0.005, 0.005, and 0.013, respectively). The receiver operating characteristic analysis revealed that area under the curve was significantly increased after adding the combined unfavorable genotype score to the model containing the known clinicopathologic factors. CONCLUSIONS: Our results suggest that SNPs in Notch pathway genes may be predictors of cutaneous melanoma disease-specific survival. IMPACT: Our discovery offers a translational potential for using genetic variants in Notch pathway genes as a genotype score of biomarkers for developing an improved prognostic assessment and personalized management of cutaneous melanoma patients.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/25953768

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1055-9965.EPI-14-1380-T

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1538-7755

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https://hdl.handle.net/10161/10668

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eng

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American Association for Cancer Research (AACR)

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Cancer Epidemiol Biomarkers Prev

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10.1158/1055-9965.EPI-14-1380-T

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Adolescent

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Adult

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Aged

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Aged, 80 and over

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Amyloid Precursor Protein Secretases

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DNA, Neoplasm

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DNA-Binding Proteins

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Female

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Genetic Variation

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Genome-Wide Association Study

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Genotype

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Humans

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Male

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Melanoma

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Membrane Glycoproteins

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Middle Aged

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Nuclear Proteins

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Nuclear Receptor Co-Repressor 2

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Polymorphism, Genetic

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Prognosis

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Survival Rate

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Texas

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Transcription Factors

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Young Adult

dc.title

Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma.

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Journal article

duke.contributor.orcid

Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/25953768

pubs.begin-page

1101

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1110

pubs.issue

7

pubs.organisational-group

Clinical Science Departments

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Medicine

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Medicine, Medical Oncology

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School of Medicine

pubs.publication-status

Published

pubs.volume

24

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