The Role Of Notch Signaling Pathway In Cutaneous Malignant Melanoma And Expression Of Its Receptors And Ligands

Background:Cutaneous malignant melanoma (CMM) is one of the most common malignant tumors. The molecular mechanism of the carcinogenesis and progression of CMM have not been clarified. Notch signaling pathway is an evolutionarily highly conserved mechanism, which controls cell differentiation and proliferation, and plays an important role in embryogenesis and many types of cell fate determination. There are reports showing that Notch signaling is also involved in the development of some cancers. The deregulation of Notch receptors and ligands and the aberrant activation of Notch signaling are found in a serial of malignant tumors.Objective:To study expression of Notch1, Notch4, Jagged1 and D114 by immunohistochemical methods. It will help us to understand their role and relationship, and to explore the Notch signaling pathway effect in the pathogenesis of CMM.Methods:Formalin fixed paraffin embedded tissue samples of 40 patients with cutaneous malignant melanoma and 15 patients with melanocytic nevus were immunohistochemically stained to detect the expression pattern and intensity of Notch1, Notch4, Jagged1 and D114. Software SPSS 21.0 was used to analyse the data.Results:In primary malignant melanoma, the expression of Notch1, Notch4, Jagged1 and D114 were positive, while in melanocytic nevus, the expression of Notch1, Notch4, Jagged1 and D114 were negative. There was significant statistical difference in expression of Notch4, Jagged1 and D114 between the group of primary MM in situ and the invasion group, but there was no significant difference in Notch1. There was significant statistical difference in expression of Notch1, Notch4, Jagged1 and D114 between the group of primary MM and melanocytic nevus. The expression of Notchl and Jaggedl was positively correlated(rs=0.350, P=0.027), as well as the expression of Notch1 and D114 (rs=0.562, P=0.000), while the expression of Jagged1 and D114 was negatively correlated(rs=-0.734, P=0.000). The results suggested that Notch1, Notch4, Jagged1 and D114 may participate in the development of MM.Conclusion:Our study initially indicates that Notch signaling pathway may be one of the pathogenesis of MM. Further research in vitro needs to be done to explore the detailed mechanism of the notch pathway.