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pmid:35154512

Identification of the Relationship between Hub Genes and Immune Cell Infiltration in Vascular Endothelial Cells of Proliferative Diabetic Retinopathy Using Bioinformatics Methods.

Jing Huang · Qiong Zhou

Disease markers · 2022 doi:10.1155/2022/7231046

Paper

complete

Experiment

complete

Data

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Analysis

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title
Identification of the Relationship between Hub Genes and Immune Cell Infiltration in Vascular Endothelial Cells of Proliferative Diabetic Retinopathy Using Bioinformatics Methods.
doi
10.1155/2022/7231046
pmid
35154512
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[0]
Jing Huang
[1]
Qiong Zhou
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Disease markers
year
2022
abstract
BACKGROUND: Diabetic retinopathy (DR) is a serious ophthalmopathy that causes blindness, especially in the proliferative stage. However, the pathogenesis of its effect on endothelial cells, especially its relationship with immune cell infiltration, remains unclear. METHODS: The dataset GSE94019 was downloaded from the Gene Expression Omnibus (GEO) database to obtain DEGs. Through aggregate analyses such as Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis, a protein-protein interaction (PPI) network was constructed to analyze the potential function of DEGs. Weighted gene coexpression network analysis (WGCNA) and Cytoscape software including molecular complex detection (MCODE) and cytoHubba plug-ins were used to comprehensively analyze and determine the hub genes. ImmuCellAI analysis was performed to further study the relationship between samples, hub genes, and 24 types of immune cell infiltration. Finally, gene-set enrichment analysis (GSEA) was employed to identify the enrichment of immune cell infiltration and endothelial cell phenotype modifications in GO biological processes (BP) based on the expression level of hub genes. RESULTS: 2393 DEGs were identified, of which 800 genes were downregulated, and 1593 genes were upregulated. The results of functional enrichment revealed that 1398 BP terms were significantly enriched in DEGs. Three hub genes, EEF1A1, RPL11, and RPS27A, which were identified by conjoint analysis using WGCNA and Cytoscape software, were positively correlated with the number of CD4 naive T cells and negatively correlated with the numbers of B cells. The number of CD4 naive T cells, T helper 2 (Th2) cells, and effector memory T (Tem) cells were significantly higher while CD8 naive T cells and B cells significantly were lower in the diabetic group than in the nondiabetic group. CONCLUSIONS: We unearthed the DEGs and Hub genes of endothelial cells related to the pathogenesis of PDR: EEF1A1, RPL11, and RPS27A, which are highly related to each other and participate in the specific biological process of inflammation-related immune cell infiltration and endothelial cell development, chemotaxis, and proliferation, thus providing new perspectives into the diagnosis of and potential "killing two birds with one stone" targeted therapy for PDR.
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RNA-seq data processing and normalization were performed using the edgeR package with trimmed-mean of M values (TMM) modus [32].
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RNA-seq data processing and normalization were performed using the edgeR package with trimmed-mean of M values (TMM) modus [32].
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Using EdgeR, the study identified 2393 differentially expressed genes between proliferative diabetic retinopathy fibrovascular membrane endothelial cells and nondiabetic retinal endothelial cells, including 1593 upregulated and 800 downregulated genes.
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Using the EdgeR package, a total of 2393 DEGs were identified, of which 1593 genes were upregulated and 800 were downregulated.
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Using EdgeR, the study identified 2393 differentially expressed genes between proliferative diabetic retinopathy fibrovascular membrane endothelial cells and nondiabetic retinal endothelial cells, including 1593 upregulated and 800 downregulated genes.
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Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35154512", "kind": "science-record", "revision": 6, "content_hash": "sha256:571f886fcdbed695bed7b868eaffef03e7350b5db46278164da2caf51b98a1c6", "created_at": "2026-11-01T17:36:54Z", "updated_at": "2026-11-01T22:48:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of the Relationship between Hub Genes and Immune Cell Infiltration in Vascular Endothelial Cells of Proliferative Diabetic Retinopathy Using Bioinformatics Methods.", "doi": "10.1155/2022/7231046", "pmid": "35154512", "authors": ["Jing Huang", "Qiong Zhou"], "journal": "Disease markers", "year": 2022, "abstract": "BACKGROUND: Diabetic retinopathy (DR) is a serious ophthalmopathy that causes blindness, especially in the proliferative stage. However, the pathogenesis of its effect on endothelial cells, especially its relationship with immune cell infiltration, remains unclear.\nMETHODS: The dataset GSE94019 was downloaded from the Gene Expression Omnibus (GEO) database to obtain DEGs. Through aggregate analyses such as Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis, a protein-protein interaction (PPI) network was constructed to analyze the potential function of DEGs. Weighted gene coexpression network analysis (WGCNA) and Cytoscape software including molecular complex detection (MCODE) and cytoHubba plug-ins were used to comprehensively analyze and determine the hub genes. ImmuCellAI analysis was performed to further study the relationship between samples, hub genes, and 24 types of immune cell infiltration. Finally, gene-set enrichment analysis (GSEA) was employed to identify the enrichment of immune cell infiltration and endothelial cell phenotype modifications in GO biological processes (BP) based on the expression level of hub genes.\nRESULTS: 2393 DEGs were identified, of which 800 genes were downregulated, and 1593 genes were upregulated. The results of functional enrichment revealed that 1398 BP terms were significantly enriched in DEGs. Three hub genes, EEF1A1, RPL11, and RPS27A, which were identified by conjoint analysis using WGCNA and Cytoscape software, were positively correlated with the number of CD4 naive T cells and negatively correlated with the numbers of B cells. The number of CD4 naive T cells, T helper 2 (Th2) cells, and effector memory T (Tem) cells were significantly higher while CD8 naive T cells and B cells significantly were lower in the diabetic group than in the nondiabetic group.\nCONCLUSIONS: We unearthed the DEGs and Hub genes of endothelial cells related to the pathogenesis of PDR: EEF1A1, RPL11, and RPS27A, which are highly related to each other and participate in the specific biological process of inflammation-related immune cell infiltration and endothelial cell development, chemotaxis, and proliferation, thus providing new perspectives into the diagnosis of and potential \"killing two birds with one stone\" targeted therapy for PDR.", "claims": [{"id": "claim-method", "statement": "RNA-seq data processing and normalization were performed using the edgeR package with trimmed-mean of M values (TMM) modus [32].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35154512", "locator": "sections[4] \"2.2. Analysis of Differential Expression\" paragraph 2", "quote": "RNA-seq data processing and normalization were performed using the edgeR package with trimmed-mean of M values (TMM) modus [32]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during the current study are available in Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35154512", "locator": "sections[23] \"Data Availability\" paragraph 2", "quote": "The datasets analyzed during the current study are available in Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using EdgeR, the study identified 2393 differentially expressed genes between proliferative diabetic retinopathy fibrovascular membrane endothelial cells and nondiabetic retinal endothelial cells, including 1593 upregulated and 800 downregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35154512", "locator": "sections[13] \"3.1. Identification of DEGs\" paragraph 2", "quote": "Using the EdgeR package, a total of 2393 DEGs were identified, of which 1593 genes were upregulated and 800 were downregulated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using EdgeR, the study identified 2393 differentially expressed genes between proliferative diabetic retinopathy fibrovascular membrane endothelial cells and nondiabetic retinal endothelial cells, including 1593 upregulated and 800 downregulated genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35154512"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102485"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102485"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35154512", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/7231046", "sha256": 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"structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed during the current study are available in Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2739339", "GSM2739340", "GSM2739341", "GSM2739342", "GSM2739343", "GSM2739344", "GSM2739345", "GSM2739346", "GSM2739347", "GSM2739348", "GSM2739349", "GSM2739350", "GSM2739351", "GSM2739352", "GSM2739353", "GSM2739354", "GSM2739355", "GSM2739356", "GSM2739357", "GSM2739358", "GSM2739359", "GSM2739360", "GSM2739361", "GSM2739362", "GSM2739363", "GSM2739364", "GSM2739365", "GSM2739366", "GSM2739367", "GSM2739368"], "sample_count": 30, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE142025", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE142025", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE142025", "version": null, "note": "The datasets analyzed during the current study are available in Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed during the current study are available in Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4217781", "GSM4217782", "GSM4217783", "GSM4217784", "GSM4217785", "GSM4217786", "GSM4217787", "GSM4217788", "GSM4217789", "GSM4217790", "GSM4217791", "GSM4217792", "GSM4217793", "GSM4217794", "GSM4217795", "GSM4217796", "GSM4217797", "GSM4217798", "GSM4217799", "GSM4217800", "GSM4217801", "GSM4217802", "GSM4217803", "GSM4217804", "GSM4217805", "GSM4217806", "GSM4217807", "GSM4217808", "GSM4217809", "GSM4217810", "GSM4217811", "GSM4217812", "GSM4217813", "GSM4217814", "GSM4217815", "GSM4217816"], "sample_count": 36, "group_sizes": null, "group_sizes_basis": null, "platform": "20301", "taxon": "Homo sapiens", "title": "Comparison of Kidney Transcriptomic Profiles of Early and Advanced Diabetic Nephropathy Reveals Potential New Mechanisms for Disease Progression", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE94019", "role": "raw", "format": 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