Dataset Information

Transcriptome and proteome analysis of the human corneal endothelium and aqueous humor reveal endothelial cell dysfunction markers

ABSTRACT: Background: The underlying mechanism as well as diagnostic molecular biomarkers for corneal endothelial cell dysfunction (CECD) remain elusive. This study aimed to elucidate molecular mechanism of CECD via proteomic and transcriptomic approaches and identify novel biomarkers in aqueous humor (AH) directly associated with changes in CECs. Methods: We carried out an in-depth proteomic analysis of patient-derived AH as well as transcriptomic analysis of CECs from the same patients with bullous keratopathy (BK) resulting from CECD. Selected candidate proteins were further verified by individual data-independent acquisition and immunoassay using further AH samples from CECD patients. Findings: Using integrated multi-omics analysis, systematic alterations of proteins in AH and mRNA in CECs were mainly associated with the immune mechanism during BK development. Through individual proteomic verification via DIA analysis, three AH proteins were determined as potential predictive markers including TIMP1, FCGBP, and ANGPTL7. Finally, we confirmed these biomarkers using immunoassay in individual AH samples of CECD. Interpretation: Our multi-omics analysis may provide valuable insights into the disease-specific process as well as possibility of biofluid biomarkers in CECD. Further investigation with large scale is required to determine whether AH biomarkers are useful as liquid biopsy targets for the assessment of CEC function

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Jae Hun Jung

LAB HEAD: Jae Hun Jung

PROVIDER: PXD023772 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction.

Moon Chae-Eun CE Kim Chang Hwan CH Jung Jae Hun JH Cho Young Joo YJ Choi Kee Yong KY Han Kyusun K Seo Kyoung Yul KY Lee Hyung Keun HK Ji Yong Woo YW

International journal of molecular sciences 20231019 20

Earlier studies have reported that elevated protein levels in the aqueous humor (AH) are associated with corneal endothelial cell dysfunction (CECD), but the details of the underlying mechanism as well as specific biomarkers for CECD remain elusive. In the present study, we aimed to identify protein markers in AH directly associated with changes to corneal endothelial cells (CECs), as AH can be easily obtained for analysis. We carried out an in-depth proteomic analysis of patient-derived AH as w ...[more]

PMID: 37895034

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Project description:Glaucoma is a group of diseases characterized by progressive optic nerve damage leading to irreversible visual field loss, often associated with elevated intraocular pressure (IOP). However, the specific underlying factors or molecular mechanisms distinguishing various glaucoma subtypes are still not fully understood. In this study, we enrolled a total of 27 subjects, comprising 5 exfoliation syndrome (XFS), 4 exfoliation glaucoma (XFG), 11 primary open-angle glaucoma (POAG), and 7 cataract patients (Control) for a comparative multi-omics analysis including both proteomics and metabolomics of the aqueous humor (AH). The AH proteome and metabolome were analyzed separately using data-independent acquisition (DIA) and data-dependent acquisition (DDA) methods, after which the results were additionally integrated for a comprehensive analysis. The comparative proteomics analysis led to the identification of differentially expressed proteins (DEPs) related to lipid metabolism, complement activation, and extracellular matrix (ECM) regulation, which were commonly up-regulated in both XFG and POAG groups. The metabolomics analysis revealed differentially expressed metabolites (DEMs) particularly those involved in amino acids, suggesting their role in antioxidative processes. Thus, bioinformatic analysis suggested significant substances, such as VTN, APOA1, C6, and L-phenylalanine, that showed quantitative alterations in glaucoma patients. In addition, the integrating the individual omics analyses revealed interaction networks involving PLG, APOA1, and L-phenylalanine, or C3, APOD, and L-valine, suggesting the quantitative relationship in protein-metabolite interactions related to inflammation and lipid metabolism within the AH of glaucoma patients. Furthermore, the correlation approach identified a relationship between FGG and L-phenylalanine, and VTN and inosine, implying potential interactions among compounds not previously identified. These findings would provide valuable insights into the complex molecular mechanism differentiating glaucoma subtypes and may benefit further research into the clinical application of AH proteome and metabolome.

Project description:There has been a great deal of interest in identifying potential biomarkers of aging (Butler et al. 2004). Biomarkers of aging would be useful to predict potential vulnerabilities in an individual that may arise well before they are chronologically expected, due to idiosyncratic aging rates that occur between individuals. Prior attempts to identify biomarkers of aging have often relied on the comparisons of long-lived animals to a wild-type control (Dhahbi et al. 2004). However, the effect of interventions in model systems that prolong lifespan (such as single gene mutations, or caloric restriction) can sometimes be difficult to interpret due to the manipulation itself having multiple unforeseen consequences on physiology, unrelated to aging itself (Gems et al. 2002; Partridge & Gems 2006). The search for predictive biomarkers of aging therefore is problematic, and the identification of metrics that can be used to predict either physiological or chronological age would be of great value (Butler et al. 2004). One methodology which has been used to identify biomarkers for numerous pathologies is gene expression profiling. Here, we report whole-genome expression profiles of individual wild-type Caenorhabditis elegans covering the entire wild-type nematode life span. Individual nematodes were scored for either age-related behavioral phenotypes, or survival, and then subsequently associated with their respective gene expression profiles. This facilitated the identification of transcriptional profiles that were highly associated with either physiological or chronological age. Overall, our approach serves as a paradigm for identifying potential biomarkers of aging in higher organisms that can be repeatedly sampled throughout their lifespan. The full normalized data set with expression values for all genes of all individual worms at all ages (104 worms/arrays) is available as a 28Mb download as a supplementary file on this page (GSE12290.txt). Keywords: time couse Time course of aging in C. elegans. 7 ages were assayed, with a minimum of 9 biological replicates per timepoint, and as many as 17 biological replicates. All ages were compared to an independent 4 day old (young) pooled control.

Dataset Information

Transcriptome and proteome analysis of the human corneal endothelium and aqueous humor reveal endothelial cell dysfunction markers

Publications

Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction.

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