American Association for Cancer Research
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Supplemental Table S1-S5 from Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma

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posted on 2023-03-31, 13:47 authored by Weikang Zhang, Hongliang Liu, Zhensheng Liu, Dakai Zhu, Christopher I. Amos, Shenying Fang, Jeffrey E. Lee, Qingyi Wei

Supplemental Table S1-S5. Table S1. List of 4,949 common genotyped and imputed SNPs in the Notch signaling pathway. Table S2. List of 78 common SNPs in the Notch signaling pathway found to be associated with CM DSS with FPRP<0.2 Table S3. Predictors of DSS in CM patients obtained from stepwise cox regression analysis of selected variables. Table S4. Association between selected SNPs in the Notch pathway genes and OS of CM patients. Table S5. Stratified association analyses on OS and HRs for CM patients with different numbers of unfavorable genotypes across genes in the Notch pathway.



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. Cancer Epidemiol Biomarkers Prev; 24(7); 1101–10. ©2015 AACR.

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