Uveal melanoma metastases are lethal and remain incurable. A quantitative proteomic analysis of 53 metastasizing and 47 non-metastasizing primary
uveal melanoma (pUM) was pursued for insights into UM
metastasis and
protein biomarkers. The metastatic status of the pUM specimens was defined based on clinical data, survival histories, prognostic analyses, and liver histopathology. LC MS/MS iTRAQ technology, the Mascot search engine, and the UniProt human database were used to identify and quantify pUM
proteins relative to the normal choroid excised from UM donor eyes. The determined
proteomes of all 100
tumors were very similar, encompassing a total of 3935 pUM
proteins.
Proteins differentially expressed (DE) between metastasizing and non-metastasizing pUM (n = 402) were employed in bioinformatic analyses that predicted significant differences in the immune system between metastasizing and non-metastasizing pUM. The immune
proteins (n = 778) identified in this study support the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1,
HLA-DPA1, and several DE immune
kinases and
phosphatases as possible candidates for immune
therapy checkpoint blockade. Prediction modeling identified 32
proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy, supporting the potential for
protein-based prognostic methods for detecting UM
metastasis.