Quantitative proteomic analysis of uveal melanoma reveals potential therapeutic targets

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Abstract

Purpose

To identify potential therapeutic targets in uveal melanoma by global proteomic analysis of tumours with high- (HR) or low- (LR) risk of developing metastatic disease.

Methods

Proteins were extracted from fresh-frozen tissues from 10 HR and 10 LR UM and from 22 normal choroid samples, subjected to isobaric tagging for relative quantification (iTRAQ) and analysed by nanoLC-MS/MS. Peptide identification was performed using Protein Pilot with a False Discovery Rate set at 5%. Differential expression of proteins and their relative abundance between the groups was investigated by supervised and unsupervised hierarchical clustering and outlier analyses.

Results

We identified 2651 unique proteins. Compared to normal choroid, the tumours showed 672 proteins up-regulated more than 1.5-fold and 459 down-regulated more than 1.5-fold. Of these, 18 proteins with known functions in tumour development/progression were identified and shown to be differentially expressed between HR and LR samples. Four of these have been further validated by immunohistochemistry in a larger cohort of patient samples.

Conclusion

Using quantitative proteomic analysis and immunohistochemistry we have identified novel potential therapeutic targets in UM. One of these in particular is a tumour suppressor associated with chemosensitivity in other cancers, but not yet described in UM. This opens a novel therapeutic avenue that is being further investigated.

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