Gene Biomarkers Related to Th17 Cells in Macular Edema of Diabetic Retinopathy: Cutting-Edge Comprehensive Bioinformatics Analysis and In Vivo Validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35651615", "kind": "science-record", "revision": 4, "content_hash": "sha256:9dd9c63948e63745a05087d2e5f5564eec0c4a74aff5cd849d3a2c6de96d007f", "created_at": "2026-11-01T18:14:35Z", "updated_at": "2026-11-01T22:06:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Gene Biomarkers Related to Th17 Cells in Macular Edema of Diabetic Retinopathy: Cutting-Edge Comprehensive Bioinformatics Analysis and In Vivo Validation.", "doi": "10.3389/fimmu.2022.858972", "pmid": "35651615", "authors": ["Jing Huang", "Qiong Zhou"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "Background: Previous studies have shown that T-helper 17 (Th17) cell-related cytokines are significantly increased in the vitreous of proliferative diabetic retinopathy (PDR), suggesting that Th17 cells play an important role in the inflammatory response of diabetic retinopathy (DR), but its cell infiltration and gene correlation in the retina of DR, especially in diabetic macular edema (DME), have not been studied.\nMethods: The dataset GSE160306 was downloaded from the Gene Expression Omnibus (GEO) database, which contains 9 NPDR samples and 10 DME samples. ImmuCellAI algorithm was used to estimate the abundance of Th17 cells in 24 kinds of infiltrating immune cells. The differentially expressed Th17 related genes (DETh17RGs) between NPDR and DME were documented by difference analysis and correlation analysis. 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 DETh17RGs. CytoHubba plug-in algorithm, Lasso regression analysis and support vector machine recursive feature elimination (SVM-RFE) were implemented to comprehensively identify Hub DETh17RGs. The expression archetypes of Hub DETh17RGs were further verified in several other independent datasets related to DR. The Th17RG score was defined as the genetic characterization of six Hub DETh17RGs using the GSVA sample score method, which was used to distinguish early and advanced diabetic nephropathy (DN) as well as normal and diabetic nephropathy. Finally, real-time quantitative PCR (qPCR) was implemented to verify the transcription levels of Hub DETh17RGs in the STZ-induced DR model mice (C57BL/6J).\nResults: 238 DETh17RGs were identified, of which 212 genes were positively correlated while only 26 genes were negatively correlated. Six genes (CD44, CDC42, TIMP1, BMP7, RHOC, FLT1) were identified as Hub DETh17RGs. Because DR and DN have a strong correlation in clinical practice, the verification of multiple independent datasets related to DR and DN proved that Hub DETh17RGs can not only distinguish PDR patients from normal people, but also distinguish DN patients from normal people. It can also identify the initial and advanced stages of the two diseases (NPDR vs DME, Early DN vs Advanced DN). Except for CDC42 and TIMP1, the qPCR transcription levels and trends of other Hub DETh17RGs in STZ-induced DR model mice were consistent with the human transcriptome level in this study.\nConclusion: This study will improve our understanding of Th17 cell-related molecular mechanisms in the progression of DME. At the same time, it also provides an updated basis for the molecular mechanism of Th17 cell crosstalk in the eye and kidney in diabetes.", "claims": [{"id": "claim-method", "statement": "In this study, the Hub DETh17RGs were integrated as the set of characteristic genes to participate in each validation dataset, and the R package GSVA was used to calculate the GSVA enrichment score for each sample, which we define as the “Th17RG score”. The package pROC in R was performed to analyze and assess the diagnostic value of the Hub DETh17RGs in GSE30528 and GSE96804 using receiver operating characteristic (ROC) curves and reckoning the area under the curve (AUC).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35651615", "locator": "sections[10] \"GSVA Constructs Hub DETh17RGs Diagnostic Features\" paragraph 2", "quote": "In this study, the Hub DETh17RGs were integrated as the set of characteristic genes to participate in each validation dataset, and the R package GSVA was used to calculate the GSVA enrichment score for each sample, which we define as the “Th17RG score”."}, {"asset": "source:pmid:35651615", "locator": "sections[10] \"GSVA Constructs Hub DETh17RGs Diagnostic Features\" paragraph 2", "quote": "The package pROC in R was performed to analyze and assess the diagnostic value of the Hub DETh17RGs in GSE30528 and GSE96804 using receiver operating characteristic (ROC) curves and reckoning the area under the curve (AUC)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35651615", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The six-gene GSVA-derived Th17RG score showed diagnostic value for diabetic nephropathy, with AUCs of 82% and 74% in GSE30528 and GSE96804, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35651615", "locator": "sections[18] \"Diagnostic Value of Hub DETh17RGs Features in DN\" paragraph 2", "quote": "ROC analysis showed that the AUC of GSE30528 and GSE96804 reached 82% and 74%, respectively, which could be considered to have a high degree of differentiation (Figures 6C, D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The six-gene GSVA-derived Th17RG score showed diagnostic value for diabetic nephropathy, with AUCs of 82% and 74% in GSE30528 and GSE96804, respectively.", "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:35651615"], "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. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:35651615", "data:geo:GSE102485"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE102485"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:48:35Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 20270, "completion_tokens": 2001, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:35651615", "type": "paper", "label": "pmid:35651615"}, {"id": "source:pmid:35651615", "type": "manuscript", "label": "PMID 35651615 full text"}, {"id": "data:geo:GSE102485", "type": "dataset", "label": "GEO GSE102485"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35651615", "type": "paper", "label": "pmid:35651615"}, {"id": "source:pmid:35651615", "type": "manuscript", "label": "PMID 35651615 full text"}, {"id": "data:geo:GSE102485", "type": "dataset", "label": "GEO GSE102485"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35651615", "type": "extraction", "used": ["source:pmid:35651615"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE102485", "type": "accession_resolution", "used": ["data:geo:GSE102485"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:35651615", "parent_hash": "sha256:216b11b4d17a12476ddbd77cfb56d056d6f110d9d496c628aec195f7b351231e", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE102485 licence not read", "asset:data:geo:GSE102485 not downloaded", "asset:data:geo:GSE142025 licence not read", "asset:data:geo:GSE142025 not downloaded", "asset:data:geo:GSE160306 licence not read", "asset:data:geo:GSE160306 not downloaded", "asset:data:geo:GSE30528 licence not read", "asset:data:geo:GSE30528 not downloaded", "asset:data:geo:GSE60436 licence not read", "asset:data:geo:GSE60436 not downloaded", "asset:data:geo:GSE94019 licence not read", "asset:data:geo:GSE94019 not downloaded", "asset:data:geo:GSE96804 licence not read", "asset:data:geo:GSE96804 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ge Comprehensive Bioinformatics Analysis and In Vivo Validation.", "other Hub DETh17RGs in STZ-induced DR model mice were consistent with the human transcriptome leve"], "order_basis": "paper_text_order:90", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["opathy. Finally, real-time quantitative PCR (qPCR) was implemented to verify the transcription", "dvanced DN). Except for CDC42 and TIMP1, the qPCR transcription levels and trends of other Hub", "as normal and diabetic nephropathy. Finally, real-time quantitative PCR (qPCR) was implemented to verify the transcr"], "order_basis": "paper_text_order:1719", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["DR model mice were consistent with the human transcriptome level in this study. Conclusion: This study", "ating immune cells including Th17 cells from RNA-seq digital gene expression matrix data and to o"], "order_basis": "paper_text_order:2622", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}