Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma
Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Genetics | Molecular Biology | Neoplasms
PURPOSE: The development of a genetic signature for the identification of high-risk cutaneous melanoma tumors would provide a valuable prognostic tool with value for stage I and II patients who represent a remarkably heterogeneous group with a 3% to 55% chance of disease progression and death 5 years from diagnosis.
EXPERIMENTAL DESIGN: A prognostic 28-gene signature was identified by analysis of microarray expression data. Primary cutaneous melanoma tumor tissue was evaluated by RT-PCR for expression of the signature, and radial basis machine (RBM) modeling was performed to predict risk of metastasis.
RESULTS: RBM analysis of cutaneous melanoma tumor gene expression reports low risk (class 1) or high risk (class 2) of metastasis. Metastatic risk was predicted with high accuracy in development (ROC = 0.93) and validation (ROC = 0.91) cohorts of primary cutaneous melanoma tumor tissue. Kaplan-Meier analysis indicated that the 5-year disease-free survival (DFS) rates in the development set were 100% and 38% for predicted classes 1 and 2 cases, respectively (P < 0.0001). DFS rates for the validation set were 97% and 31% for predicted classes 1 and 2 cases, respectively (P < 0.0001). Gene expression profile (GEP), American Joint Committee on Cancer stage, Breslow thickness, ulceration, and age were independent predictors of metastatic risk according to Cox regression analysis.
CONCLUSIONS: The GEP signature accurately predicts metastasis risk in a multicenter cohort of primary cutaneous melanoma tumors. Preliminary Cox regression analysis indicates that the signature is an independent predictor of metastasis risk in the cohort presented.
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Citation: Clin Cancer Res. 2015 Jan 1;21(1):175-83. doi: 10.1158/1078-0432.CCR-13-3316. Link to article on publisher's site
Gerami, Pedram; Cook, Robert W.; Wilkinson, Jeff; Russell, Maria C.; Dhillon, Navneet; Amaria, Rodabe N.; Gonzalez, Rene; Lyle, Stephen; Johnson, Clare E.; Oelschlager, Kristen M.; Jackson, Gilchrist L.; Greisinger, Anthony J.; Maetzold, Derek; Delman, Keith A.; Lawson, David H.; and Stone, John F., "Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma" (2015). Molecular, Cell and Cancer Biology Publications. 19.