Fig. 5. Differential expression of MKI67, CDK2, and FABP5 retrospectively predicts melanoma patient survival.

(A) Kaplan-Meier survival curves from 473 patients with melanoma after stratification into low, medium (med.), and high and top expression quartiles of PRAME, MKI67, CDK2, and FABP5. Rightmost curve shows the comparatively increased differential survival stratification using the sum of log₂ MKI67, CDK2, and FABP5 expression. Cox (proportional hazards) regression analyses HRs with their respective P values are shown below each Kaplan-Meier curve. The Cox regression analyses were based on a model that included gene expression values, patient age, gender, and tumor stage as covariates. The analysis showed that expression of MKI67, CDK2, and FABP5 was statistically significant and independent predictors of poor prognosis. (B) UMAP shows combinatorial overlap of MKI67-, CDK2-, and FABP5-expressing cells enriched in the metastatic melanoma cell clusters f, g, and h identified in Fig. 2. (C) The panels show comparative increased expression of CDK2 and FABP5 in metastatic melanoma compared to nevus, both at the RNA and protein level. White and black bordered rectangles are magnified in adjacent panels as shown. White open and black arrowheads show expression of FABP5 RNA and protein in the upper layers of the epidermis. Green open arrows show normal, physiologic melanin visible in both H&E- and IHC-processed tissue sections. Green closed arrow shows atypical mitotic figure within metastatic melanoma. (D) Protein expression of PRAME, CDK2, and FABP5 highlight malignant melanoma metastasized to lymph node. (E) scRNA expression following cell cycle inhibition using CDK4/6 inhibitor abemaciclib or control (DMSO) in melanoma IGR37 (top row) and UACC-257 (bottom row) cell lines. The t-SNE plots show loss of MKI67 expression, partial loss of FABP5, and comparatively little change in CDK2 expression in abemaciclib-treated cells versus control.