PLK1 (Polo-like kinase 1 (Drosophila)). Another probe for gene that ranks high as a positive marker of metastasis is PLK1, Polo-like kinase 1, Serine/Threonine protein kinase 13 (AA629262). PLK1 is a centrosomal kinase [135] which is Figure 7 . Scatter plot showing the expression of the probe corresponding to ADA (Adenosine deaminase), AA683578 (y-axis) and TP63 (Tumor protein p63), AA455929 (x-axis). All the samples that have TP63 expression are normal or nevi, with two primary melanomas still preserving TP63 expression but with higher ADA. The trend reverses for the rest of the primary melanoma samples and the metastatic ones, which all express ADA but not TP63. doi:10.1371/journal.pone.0012262.g007 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 = 20.63632) 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. doi:10.1371/journal.pone.0012262.g006 regarded as being linked to centrosome maturation and spindle assembly [135] . PLK1 expression has also been singled out as a biomarker of a ''death-from-cancer'' signature, sharing with others the function of being an activator of mitotic spindle check point proteins. With other proteins it would has a stem cell-like expression profile phenotypically characterized by enabling metastasis with anoikis resistance and disregulated cell-cycle control [136] . PLK1 inhibition could be a common target for gastric adenocarcinoma [137] , bladder cancer [138] , colon cancer [139, 140] , hepatocellular carcinoma [141] , medullary thyroid carcinoma [142] , esophageal cancer [143] , pancreatic cancer [144] and in some types of non-Hodgkin lymphomas [145] and breast cancer [146] .