Dataset Information

Uveal Melanoma Human Vitreous Proteome

ABSTRACT: The purpose of the project was to profile protein expression liquid vitreous biopsies from uveal melanoma (UM) patients using mass spectrometry, to identify prognostic biomarkers, signaling pathways, and therapeutic targets. Vitreous biopsies were collected from two cohorts: comparative control eyes with epiretinal membranes (ERM) and test eyes with UM. Samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Vitreous Humor

DISEASE(S): Uveal Melanoma

SUBMITTER: Gabriel Velez

LAB HEAD: Vinit Mahajan

PROVIDER: PXD043403 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers.

Velez Gabriel G Wolf Julian J Dufour Antoine A Mruthyunjaya Prithvi P Mahajan Vinit B VB

Investigative ophthalmology & visual science 20231101 14

<h4>Purpose</h4>The purpose of this study was to profile protein expression liquid vitreous biopsies from patients with uveal melanoma (UM) using mass spectrometry to identify prognostic biomarkers, signaling pathways, and therapeutic targets.<h4>Methods</h4>Vitreous biopsies were collected from two cohorts in a pilot study: comparative control eyes with epiretinal membranes (ERM; n = 3) and test eyes with UM (n = 8). Samples were analyzed using liquid chromatography-tandem mass spectrometry (LC ...[more]

PMID: 37955612

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Project description:Reduced oxygenation of photoreceptors and the RPE in the ageing eye may be a risk factor for the development of both neovascular and dry AMD. Chronic activation of the molecular response to hypoxia in RPE or photoreceptors leads to retinal degeneration that depends on hypoxia inducible transcription factors. For approaching the identification of accessible markers characteristic for photoreceptors with an activated hypoxic response, we used a proteomics approach to determine the protein composition of the vitreous humor in mice. To discriminate between rod and cone-specific effects we used genetically modified mice that had the hypoxic response activated specifically in rods of a rod-dominant retina (rodΔVhl) or a genetically engineered all-cone retina (coneΔVhl). For comparison, we used wild-type mice exposed for 6 hours to acute hypoxia. We identified 1,357 unique proteins in the vitreous of mice after acute hypoxia, 1,624 in rodΔVhl and 1,895 in coneΔVhl mice. Of these, 1,043 proteins were common to all three types of mice. Of the identified proteins, 257 were significantly regulated by a factor of 1.5 or more in hypoxic mice, 258 in rodΔVhl and 356 in coneΔVhl mice in at least one of the three analyzed time points. Only 51 of the significantly regulated proteins were common to the vitreous of rodΔVhl and coneΔVhl mice, suggesting different consequences of the activated hypoxic response for rods and cones. Guanylate binding protein 2 (GBP2) was found at increased levels in the vitreous of both rodΔVhl and coneΔVhl mice at all time points tested. This was also reflected by increased gene expression in the retina. Although retinal expression of the AMD-associated gene alpha-2 macroglobulin (A2M) appeared increased in both types of mice, the protein was only found elevated in the vitreous of rodΔVhl mice. Other proteins found increased included Serpina3n, synaptosome associated protein 25 (SNAP25) and others. The distinct protein compositions present at early and late time points, suggest a well-regulated process in our models. We hypothesize that some of the proteins identified at early time points may potentially be used as markers for the chronic hypoxic response of photoreceptors.

			Action	DRS
	ERM_Case_1.mgf	Mgf
	ERM_Case_1.raw	Raw
	ERM_Case_2.mgf	Mgf
	ERM_Case_2.raw	Raw
	ERM_Case_3.mgf	Mgf