SPP1 -Secreted phosphoprotein 1 (osteopontin). SPP1 is one of the most conspicuous melanoma biomarkers [198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222] (see also the references cited in Figure 6 and note its eminent position in this scatter plot). In 1990, Craig et al. reported that SPP1 may work as an autocrine adhesion factor for tumor cells (see also [204, 223, 224] ). They observed that ''SPP1 mRNA, which is barely detectable in normal mouse epidermis, was expressed at moderate-to-high levels in 2 of 3 epidermal papillomas and at consistently high levels in 7 of 7 squamous-cell carcinomas induced by an initiation-promotion regimen'' [225] . The evidence is being constantly expanded on the role of SPP1 as a molecular prognostic biomarker in melanoma [226] . Activation of SPP1 may be an important event that allows the transformed melanocytes to invade the dermis as proposed by Geissinger et al. in 2002 [208] . This causes SPP1 to avoid the apoptotic stimulus, one of the ''hallmarks of cancer'', which invasive cells will be receiving from this new tissue.