Abstract A33: Loss of tumor suppressors KAI1 and p27 identifies a unique subgroup of primary melanoma patients with poor survival

Abstract

Abstract Objective: Melanoma is a highly heterogeneous disease. A certain subgroup of patients with primary melanomas exhibits a greater potential to develop metastatic disease and thus has worse survival. The present study attempts to identify the molecular features shared by metastatic melanomas and the subgroup of primary melanomas, and use the information to assist clinicians to design personalized therapy for primary melanoma patients. Patients and methods: Seven previously reported biomarkers, including BRAF, Dicer, Fbw7, KAI1, MMP2, p27 and Tip60, were investigated. A training cohort with 250 melanoma patients (145 primary melanomas and 105 metastatic melanomas) and an independent cohort with 92 primary melanoma patients were used for the study. Logistic regression analysis was used to identify discriminate biomarkers of metastatic melanoma from primary melanoma. Kaplan-Meier survival and multivariate Cox proportional hazard regression analysis were performed to assess the significance of the molecular signature in the prognosis of melanoma. Results: In the training cohort, we found the loss expression of KAI1 and p27 to be most significant between metastatic and primary melanoma. The primary melanoma patients with loss expression of both KAI1 and p27 had poor 5-year survival in both training cohort (P = 0.002) and independent cohort (P = 0.03). Multivariate Cox regression analysis showed that the KAI1-/p27- signature was an independent factor for disease- specific survival (P = 0.004). More important, compared to KAI1 and p27 as an individual prognostic marker, the KAI1-/p27- signature is more closely associated with melanoma patient survival: the P value is 0.004 for KAI1-/p27-, and 0.044, 0.181 for KAI1 and p27, respectively. Conclusion: Loss of both KAI1 and p27 defines a subgroup of primary melanoma patients with poor prognosis, and the combination signature is better than individual biomarker. The clinical significance of KAI1 and p27 warrants further assessment in prospective clinical trials. Citation Format: Yabin Cheng, Guohong Zhang, Yun Tang, Guangdi Chen, Gholamreza Safaee, Annand Rotte, Magdalena Martinka, Kevin McElwee, Youwen Zhou. Loss of tumor suppressors KAI1 and p27 identifies a unique subgroup of primary melanoma patients with poor survival. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A33.