A scatter plot of the Spearman correlation of 14,737 probes in the Haqq et al. melanoma dataset.

We have computed the Jensen-Shannon divergence of each sample with the normal skin average. We then computed the correlation of each individual probe expression with the Jensen-Shannon divergence of each sample. As this correlation is computed on all samples, the resulting value (x-axis) was denoted as JSM0A-Spearman. Analogously, we compute the Jensen-Shannon divergence of each sample with the average metastastic profile and we also compute the correlation of each probe with this measure (y-axis). The position of one probe corresponding to the TP63 gene (Tumor protein p63, keratinocyte transcription factor KET), AA455929, is highlighted. The expression of this probe has a relatively high negative correlation with the Jensen-Shannon divergence of the normal skin type (JSM0-Spearman = −0.63632) while at the same time is has a positive correlation with the Jensen-Shannon divergence of the metastasis profile (JSM5 = 0.62138). The first probe that presents an opposite behaviour is one for ADA (Adenosine deaminase), AA683578. Probes for SPP1 (Secreted phosphoprotein 1 or Osteopontin) and PLK1 (Polo-like kinase 1 or Drosophila) are also highlighted. While PLK1 is currently less recognized as a biomarker in melanoma research, the importance of SPP1 in cutaneous pathology [315], [318], [320], [321] and in particular in melanoma [208], [209], [210], [211], [212], [214], [215], [216], [217], [218], [219], [222], [226], [264], [314], [315], [316], [317], [319], [322], [323], [324], [325], [326], [327], [328], [804], [805], [806], [807], [808], [809] is increasing. Using a 5-biomarker panel that included SPP1, Kashani-Sabet et al. used tissue microarrays on 693 melanocytic neoplasms to show that SPP1 expression collaborates significantly improving the detection of high percentage of melanomas arising in a nevus, Spitz nevi, dysplastic nevi and misdiagnosed lesions [253]. Like in the case of prostate cancer (Figure 3, in which KLK3/PSA - Prostate Specific Antigen was highlighted), our method allows the detection of important biomarkers with a high degree of concordance with current biological understanding of metastatic processes.