Dataset Information

Proteomics of aqueous humor for biomarkers discovery in retinoblastoma

ABSTRACT: Background: Recent therapeutic advances have greatly improved the eye preservation rate in patients affected by retinoblastoma (RB), however local tumor control remains more difficult in the presence of resistant and/or relapsing retinal or vitreous disease. Thus, the identification of new biomarkers is crucial to design more effective treatment approaches. Recently, technological advances have allowed to safely recover aqueous humor (AH) from patients affected by RB undergoing local treatment. Methods: in order to identify specific proteins associated to active vitreous seeding, we have performed proteomic analysis of AH samples derived from patients affected by RB in different disease stages. Fifty-five AH samples were firstly included in this study. A new widened cohort was then used to validate the proteins identified in the previous discovery set. Results: a total of 808 and 630 proteins were identified in the two analysis, respectively. Five proteins resulted more expressed in the active vitreous seeding group: C19orf57, Girdin, SRFBP, GULP-1 and DCD. These proteins are involved in cytoskeleton regulation, tumor proliferation and growth, invasion and migration of cancer cells. Conclusion: reliable prognostic biomarkers are needed to guide RB management. Proteomic analysis of AH provide a unique opportunity to identify tumor associated biomarkers in patients with RB.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Vitreous Humor

DISEASE(S): Retinoblastoma

SUBMITTER: Andrea Petretto

LAB HEAD: Andrea Petretto

PROVIDER: PXD022218 | Pride | 2023-03-10

REPOSITORIES: Pride

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Publications

Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma.

Galardi Angela A Stathopoulos Christina C Colletti Marta M Lavarello Chiara C Russo Ida I Cozza Raffaele R Romanzo Antonino A Carcaboso Angel M AM Locatelli Franco F Petretto Andrea A Munier Francis L FL Di Giannatale Angela A

International journal of molecular sciences 20221103 21

Aqueous humor (AH) can be easily and safely used to evaluate disease-specific biomarkers in ocular disease. The aim of this study was to identify specific proteins biomarkers in the AH of retinoblastoma (RB) patients at various stages of the disease. We analyzed the proteome of 53 AH samples using high-resolution mass spectrometry. We grouped the samples according to active vitreous seeding (Group 1), active aqueous seeding (Group 2), naive RB (group 3), inactive RB (group 4), and congenital cat ...[more]

PMID: 36362243

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Project description:BACKGROUND: Alcohol-related liver disease ranges from silent alcoholic steatohepatitis (sASH), an asymptomatic and compensated phenotype, to life- threatening alcoholic hepatitis (AH). A systematic comparative study of the clinical, histological and molecular features of these subtypes is lacking. METHODS : Two large cohorts of patients were recruited in an international, observational multi-center study: a retrospective cohort of patients with sASH (n=110) and a prospective cohort of patients with AH (two subgroups with n=121 and 104). sASH and AH were compared by doing clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis. FINDINGS: Age and mean alcohol intake were similar in patients with sASH vs AH. AH showed lower mean arterial pressure than sASH. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma- glutamyl transferase levels than AH. Individuals with AH demonstrated profound liver failure, lower blood pressure and increased mortality. Histologically, the grade of steatosis, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and progenitor cell expansion were more frequent among AH patients. One-year mortality was 10% in sASH and 50% in AH. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. Globally, AH patients exhibited changes in 4,921 genes, while the number of dysregulated genes in sASH patients was less pronounced -1,327-. While sASH was characterized by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. INTERPRETATION: Despite comparable daily alcohol intake, AH patients presented with worse liver function and hemodynamic status compared to sASH. Bilirubinostasis, severe fibrosis and progenitor cell expansion were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared to sASH.

Dataset Information

Proteomics of aqueous humor for biomarkers discovery in retinoblastoma

Publications

Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma.

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