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

Publication ,  Journal Article
Velez, G; Wolf, J; Dufour, A; Mruthyunjaya, P; Mahajan, VB
Published in: Invest Ophthalmol Vis Sci
November 1, 2023

PURPOSE: 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. METHODS: 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-MS/MS). Identified proteins were compared to data from a targeted multiplex ELISA proteomics platform. RESULTS: A total of 69 significantly elevated proteins were detected in the UM vitreous, including LYVE-1. LC-MS/MS identified 62 significantly upregulated proteins in UM vitreous that were not previously identified by ELISA. Analysis of differential protein expression by tumor molecular classification (gene expression profiling [GEP] and preferentially expressed antigen in melanoma [PRAME]) further identified proteins that correlated with these classifications. Patients with high-risk GEP tumors displayed elevated vitreous expression of HGFR (fold-change [FC] = 2.66E + 03, P value = 0.003) and PYGL (FC = 1.02E + 04, P = 1.72E-08). Patients with PRAME positive tumors displayed elevated vitreous expression of ENPP-2 (FC = 3.21, P = 0.04), NEO1 (FC = 2.65E + 03, P = 0.002), and LRP1 (FC = 5.59E + 02, P value = 0.01). IGF regulatory effectors were highly represented (P value = 1.74E-16). Cross-platform analysis validated seven proteins identified by ELISA and LC-MS/MS. CONCLUSIONS: Proteomic analysis of liquid biopsies may provide prognostic information supporting gene expression of tumor biopsies. The use of multiple protein detection platforms in the same patient samples increases the sensitivity of candidate biomarker detection and allows for precise characterization of the vitreous proteome.

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Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

November 1, 2023

Volume

64

Issue

14

Start / End Page

14

Location

United States

Related Subject Headings

  • Uveal Neoplasms
  • Tandem Mass Spectrometry
  • Proteomics
  • Pilot Projects
  • Ophthalmology & Optometry
  • Melanoma
  • Humans
  • Chromatography, Liquid
  • Biomarkers
  • Antigens, Neoplasm
 

Citation

APA
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ICMJE
MLA
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Velez, G., Wolf, J., Dufour, A., Mruthyunjaya, P., & Mahajan, V. B. (2023). Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers. Invest Ophthalmol Vis Sci, 64(14), 14. https://doi.org/10.1167/iovs.64.14.14
Velez, Gabriel, Julian Wolf, Antoine Dufour, Prithvi Mruthyunjaya, and Vinit B. Mahajan. “Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers.Invest Ophthalmol Vis Sci 64, no. 14 (November 1, 2023): 14. https://doi.org/10.1167/iovs.64.14.14.
Velez G, Wolf J, Dufour A, Mruthyunjaya P, Mahajan VB. Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers. Invest Ophthalmol Vis Sci. 2023 Nov 1;64(14):14.
Velez, Gabriel, et al. “Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers.Invest Ophthalmol Vis Sci, vol. 64, no. 14, Nov. 2023, p. 14. Pubmed, doi:10.1167/iovs.64.14.14.
Velez G, Wolf J, Dufour A, Mruthyunjaya P, Mahajan VB. Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers. Invest Ophthalmol Vis Sci. 2023 Nov 1;64(14):14.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

November 1, 2023

Volume

64

Issue

14

Start / End Page

14

Location

United States

Related Subject Headings

  • Uveal Neoplasms
  • Tandem Mass Spectrometry
  • Proteomics
  • Pilot Projects
  • Ophthalmology & Optometry
  • Melanoma
  • Humans
  • Chromatography, Liquid
  • Biomarkers
  • Antigens, Neoplasm