Cutaneous melanoma disease-specific survival may be predicted by the SNPs in Notch pathway genes, according to a study published online in Cancer Epidemiology, Biomarkers & Prevention.
The Notch signaling pathway promotes growth and aggressive metastatic potential of primary melanoma cells in human cutaneous melanoma.
In the study, 6,256 SNPs were identified in 48 Notch pathway genes in 858 patients with cutaneous melanoma who were previously included in a cutaneous melanoma genome-wide association dataset.
Results revealed four putative functional SNPs of Notch genes were both independently and jointly associated with predictive roles in survival of patients with cutaneous melanoma. The variant with the most significant predictive role was NCOR2 rs2342924 T>C (aHR= 2.71; 95% CI: 1.73, 4.23; Ptrend=9.62 × 10−7). The other three predictive SNPs were NCSTN rs1124379 G>A (Ptrend=0.005), NCOR2 rs10846684 G>A (Ptrend=0.005), and MAML2 rs7953425 G>A (Ptrend=0.013).
When using the receiver operating characteristic analysis curve, the area under the curve was significantly greater after adding the unfavorable genotype score to the model containing the identified clinicopathologic factors.
The study’s findings suggest that a potential exists for developing an improved prognostic assessment and personalized management approach for patients with cutaneous melanoma using these identified genetic variants as a genotype score of biomarkers.
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.