MassIVE MSV000087437

Complete Public PXD026027

Proteomics of Primary Uveal Melanoma:Insights to Metastasis and Protein Biomarkers

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Description

Uveal melanoma metastases are lethal and remain incurable. 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 normal choroid excised from UM donor eyes containing metastasizing (n=6) and non-metastasizing (n=7) pUM. The determined proteomes of all 100 tumors were very similar, encompassing a total of 3935 pUM proteins. Proteins differentially expressed (DE) (n=402) between metastasizing and non-metastasizing pUM were employed in bioinformatic analyses that predicted significant differences in the immune system between metastasizing and non-metastasizing pUM. 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 and HLA-DPA1 as candidates for immune therapy checkpoint blockade. Prediction modeling identified 32 proteins capable of predicting with 93% discriminatory accuracy metastasizing versus non-metastasizing pUM, supporting the potential of protein-based prognostic methods for detecting UM metastasis [doi:10.25345/C5HN7C] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: bioinformatics ; immune profiling ; iTRAQ ; metastasis ; prediction modeling ; quantitative proteomics ; uveal melanoma

Contact

Principal Investigators:
(in alphabetical order) 		John W Crabb, Cleveland Clinic, USA
Submitting User: jackcrabb

Publications

Jang GF, Crabb JS, Hu B, Willard B, Kalirai H, Singh AD, Coupland SE, Crabb JW.
Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers.
Cancers (Basel). Epub 2021 Jul 14.

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