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

Publication ,  Journal Article
Zhang, W; Liu, H; Liu, Z; Zhu, D; Amos, CI; Fang, S; Lee, JE; Wei, Q
Published in: Cancer Epidemiol Biomarkers Prev
July 2015

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.

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Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

July 2015

Volume

24

Issue

7

Start / End Page

1101 / 1110

Location

United States

Related Subject Headings

  • Young Adult
  • Transcription Factors
  • Trans-Activators
  • Texas
  • Survival Rate
  • Skin Neoplasms
  • Prognosis
  • Polymorphism, Genetic
  • Nuclear Receptor Co-Repressor 2
  • Nuclear Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, W., Liu, H., Liu, Z., Zhu, D., Amos, C. I., Fang, S., … Wei, Q. (2015). Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma. Cancer Epidemiol Biomarkers Prev, 24(7), 1101–1110. https://doi.org/10.1158/1055-9965.EPI-14-1380-T
Zhang, Weikang, Hongliang Liu, Zhensheng Liu, Dakai Zhu, Christopher I. Amos, Shenying Fang, Jeffrey E. Lee, and Qingyi Wei. “Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma.Cancer Epidemiol Biomarkers Prev 24, no. 7 (July 2015): 1101–10. https://doi.org/10.1158/1055-9965.EPI-14-1380-T.
Zhang W, Liu H, Liu Z, Zhu D, Amos CI, Fang S, et al. Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma. Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1101–10.
Zhang, Weikang, et al. “Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma.Cancer Epidemiol Biomarkers Prev, vol. 24, no. 7, July 2015, pp. 1101–10. Pubmed, doi:10.1158/1055-9965.EPI-14-1380-T.
Zhang W, Liu H, Liu Z, Zhu D, Amos CI, Fang S, Lee JE, Wei Q. Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma. Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1101–1110.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

July 2015

Volume

24

Issue

7

Start / End Page

1101 / 1110

Location

United States

Related Subject Headings

  • Young Adult
  • Transcription Factors
  • Trans-Activators
  • Texas
  • Survival Rate
  • Skin Neoplasms
  • Prognosis
  • Polymorphism, Genetic
  • Nuclear Receptor Co-Repressor 2
  • Nuclear Proteins