Gene expression analysis of whole blood for the biomarker discovery of malignant melanoma Free

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The melanoma staging system reveals an extraordinary heterogeneity of survival in stage II and stage III patients, with the 10-year survival rate ranging 32-64% and 28-63% in stage II and stage III patients, respectively. Although the sentinel lymph node (SLN) status is the most powerful independent prognostic factor predicting survival, SLN biopsy is extremely costly and time-consuming, and the sensitivity is limited. There is a clear need for the development of additional prognostic biomarkers to screen patients and monitor the disease activity. Peripheral whole blood is representative of many systemic processes including immune responses and cellular communications. Circulating tumor cells and circulating endothelial cells have been reported in cancer patients. We hypothesized that gene expression analysis of peripheral blood could reveal characteristic melanoma-related and host response-related profiling in melanoma patients.

Whole blood samples were obtained from 89 newly diagnosed melanoma patients (stage I to IV) and 50 normal subjects. Gene expression analysis was performed by the Source MDx high precision quantitative real-time polymerase chain reaction using a panel of 63 genes selected from the literature search and microarray analysis.

Stepwise logistic analysis of gene expression levels was performed using individual genes showing the best power to discriminate normals from melanoma patients, as starting points. Additional genes were added in a stepwise fashion and the six gene combination giving the best discrimination was identified. Using the gene PTPRK as the starting point, the addition of S100A4, PTEN, C1QB, CTNNB1 and MNDA allowed 46/50 (92%) normals and 78/89 (90%) melanoma patients to be classified accurately. These data support the hypothesis that gene expression profiles with sufficient precision and calibration can define subsets of individuals with melanoma and may be used to stage newly diagnosed patients, and monitor the response of patients to therapy.