Figure 2.

FOXM1, CENPF, Cyclin B1 and Pin1 mRNA levels correlate in malignant melanoma and associate with poor disease outcome. (a) Heatmaps showing relative z-score corrected mRNA expression profiles of Pin1, FOXM1, CENPF, Cyclin B1 and actin in three independent Oncomine data sets.^{43, 44, 48} Where applicable, the fold difference between normal skin, benign nevi and melanoma are indicated, all of which are significant (P<0.01). (b) Overview of correlation coefficients for the indicated gene expression changes from the data sets in A. Green indicates a correlation of R>0.45; P<0.01. (c) Scatter plots of a selection of the Bogunovic dataset⁴⁸ from Oncomine showing correlation between Pin1 and FOXM1, CENPF and Cyclin B1 subdivided into patient groups that lived >2 years or <1 year after detection of metastases. Bottom right: a plot indicating the cumulative score for Pin1, FOXM1, CENPF and Cyclin B1 (number of individual markers above population mean for each mRNA) vs disease outcome. Note that not all markers may be individually elevated in the group dead <1 year vs alive >2 year, but their cumulative score appears to have prognostic value. (d and e) Immunocytochemical staining for Pin1 and CENPF on sequential sections from a mouse skin of BRAF^V600E-inducible mice that spontaneously develop melanomas in time.²³ In the same animal, Pin1 and CENPF are barely expressed in the benign nevus (d), but are strongly elevated in a similar, sequential region the adjacent melanoma (e). (f) Immunocytochemical staining for Pin1 and CENPF in normal skin and a stage III human melanoma. Note that a different Pin1 antibody (mouse-derived) is used than in (e and f). Right panel; cyclin B1 staining in skin vs melanoma samples. **P<0.01.