Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although an important proportion of stage I–II patients may still develop metastasis during follow-up. The aim of this work was to discover serum biomarkers in patients diagnosed with primary melanoma that identify those at a high risk of developing metastasis during the follow-up period. Proteomic and mass spectrophotometry analysis was performed on serum obtained from patients who developed metastasis during the first years after surgery for primary tumors and compared with that from patients who remained disease-free for more than 10 years after surgery. Five proteins were selected for validation as prognostic factors in 348 melanoma patients and 100 controls by ELISA: serum amyloid A and clusterin; immune system proteins; the cell adhesion molecules plakoglobin and vitronectin and the antimicrobial protein dermcidin. Compared to healthy controls, melanoma patients have high serum levels of these proteins at the moment of melanoma diagnosis, although the specific values were not related to the histopathological stage of the tumors. However, an analysis based on classification together with multivariate statistics showed that tumor stage, vitronectin and dermcidin levels were associated with the metastatic progression of patients with early-stage melanoma. Although melanoma patients have increased serum dermcidin levels, the REPTree classifier showed that levels of dermcidin <2.98 μg/ml predict metastasis in AJCC stage II patients. These data suggest that vitronectin and dermcidin are potent biomarkers of prognosis, which may help to improve the personalized medical care of melanoma patients and their survival.What's new?
The discovery of serum biomarkers capable of predicting metastatic risk during post-operative follow-up in early-stage primary melanoma patients could significantly benefit patient prognosis and survival. The present study identifies two promising biomarker candidates: vitronectin and dermcidin. Analysis and comparison of serum proteins in melanoma patients who either remained disease-free or developed metastases in the years after surgery to remove primary tumors revealed a strong association between metastatic progression of early-stage melanomas (AJCC stage III) and vitronectin and dermcidin serum levels. Further study of these proteins could open up new opportunities in the effort to improve long-term survival among melanoma patients.