PT  - JOURNAL ARTICLE
AU  - Filippo Mancuso
AU  - Sergio Lage
AU  - Javier Rasero
AU  - José Luis Díaz-Ramón
AU  - Aintzane Apraiz
AU  - Gorka Pérez-Yarza
AU  - Pilar Ezkurra
AU  - Cristina Penas
AU  - Ana Sánchez-Diez
AU  - María Dolores García-Vazquez
AU  - Jesús Gardeazabal
AU  - Rosa Izu
AU  - Karmele Mujika
AU  - Jesús Cortés
AU  - Aintzane Asumendi
AU  - María Dolores Boyano
TI  - A new clinical tool to predict outcome in early-stage melanoma patients
AID  - 10.1101/632455
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 632455
4099  - http://biorxiv.org/content/early/2019/05/10/632455.short
4100  - http://biorxiv.org/content/early/2019/05/10/632455.full
AB  - Around 25% of early-stage melanoma patients eventually develop metastasis. Thus, we set out to define serological biomarkers that could be used along with clinical and histopathological features of the disease to predict these events. We previously demonstrated that in stage II melanoma patients, serum levels of Dermcidin (DCD) are associated with metastatic progression. Since DCD was recently associated with a local and systemic immune response against cancer cells, the serum levels of DCD were studied using ELISA and Luminex, along with those of IL-4, IL-6, IL-10, IL-17A, IFNγ, TGFβ and GM-CSF, in order to define potential prognostic factors in a group of 448 melanoma patients, 323 of whom were diagnosed as stages I-II according AJCC. The data were analyzed employing machine learning and Kaplan-Meier techniques in order to define an algorithm that was capable of accurately classifying early stage melanoma patients with a high and low risk of developing metastasis within 2 years, the period of highest recurrence in such patients. The results show that in early stage melanoma patients and in addition to the Breslow thickness, the serum levels of the cytokines IL-4 and GM-CSF are those that best predict of melanoma metastasis. As a result, these parameters can be incorporated into a tool to discriminate subjects with a better and worse melanoma prognosis.NOVELTY AND IMPACT We have developed a prognostic equation that considers the serum IL-4 and GM-CSF values, along with the Breslow thickness to accurately classify melanoma outcome in patients. In this sense, a rigorous follow-up is recommended for early-stage melanoma patients with a high Breslow thickness, high serum IL-4 levels and low GM-CSF at the time of diagnosis, given the elevated risk that these patients will develop metastasis during follow-up.(IL)Interleukin(IFN)Interferon(TGF)Transforming Growth Factor(GM-CSF)Granulocyte-Macrophage Colony-stimulating Factor(DCD)Dermcidin(Th)T helper