The Aflibercept-Induced MicroRNA Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients Detected by Next-Generation Sequencing.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34938191", "kind": "science-record", "revision": 4, "content_hash": "sha256:824cb8ac51f114495a8ddd932f8d3dac062fcb87453ea8ed9f888a40eee264c2", "created_at": "2026-11-01T17:36:38Z", "updated_at": "2026-11-01T22:05:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Aflibercept-Induced MicroRNA Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients Detected by Next-Generation Sequencing.", "doi": "10.3389/fphar.2021.781276", "pmid": "34938191", "authors": ["Ju Guo", "Pengyi Zhou", "Zhenhui Liu", "Fangfang Dai", "Meng Pan", "Guangqi An", "Jinfeng Han", "Liping Du", "Xuemin Jin"], "journal": "Frontiers in pharmacology", "year": 2021, "abstract": "Purpose: Vascular endothelial growth factor-A (VEGF-A) is an important pathogenic factor in proliferative diabetic retinopathy (PDR), and aflibercept (Eylea) is one of the widely used anti-VEGF agents. This study investigated the microRNA (miRNA) profiles in the vitreous of 5 idiopathic macular hole patients (non-diabetic controls), 5 untreated PDR patients (no-treatment group), and 5 PDR patients treated with intravitreal aflibercept injection (treatment group). Methods: Next-generation sequencing was performed to determine the miRNA profiles. Deregulated miRNAs were validated with quantitative real-time PCR (qRT-PCR) in another cohort. The mRNA profile data (GSE160310) of PDR patients were retrieved from the Gene Expression Omnibus (GEO) database. The function of differentially expressed miRNAs and mRNAs was annotated by bioinformatic analysis and literature study. Results: Twenty-nine miRNAs were significantly dysregulated in the three groups, of which 19,984 target mRNAs were predicted. Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group versus controls, and significantly downregulated in treatment group versus no-treatment group. In the GSE160310 profile, 204 deregulated protein-coding mRNAs were identified, and finally 179 overlapped mRNAs between the 19,984 target mRNAs and 204 deregulated mRNAs were included for further analysis. Function analysis provided several roles of aflibercept-induced miRNAs, promoting the alternation of drug sensitivity or resistance-related mRNAs, and regulating critical mRNAs involved in angiogenesis and retinal fibrosis. Conclusion: Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were highly expressed in PDR patients, and intravitreal aflibercept injection could reverse this alteration. Intravitreal aflibercept injection may involve in regulating cell sensitivity or resistance to drug, angiogenesis, and retinal fibrosis.", "claims": [{"id": "claim-method", "statement": "Differentially expressed miRNAs (DEMIs) were analyzed by DEGseq, 8 and only the genes (miRNAs) with the absolute value of Log2Ratio ≥1 and Q value ≤0.01 were considered as DEMIs (Wang, Feng et al., 2010).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34938191", "locator": "sections[7] \"Bioinformatics Analysis of Sequencing Result\" paragraph 2", "quote": "Differentially expressed miRNAs (DEMIs) were analyzed by DEGseq, 8 and only the genes (miRNAs) with the absolute value of Log2Ratio ≥1 and Q value ≤0.01 were considered as DEMIs (Wang, Feng et al., 2010)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34938191", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group versus controls, and significantly downregulated in treatment group versus no-treatment group.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34938191", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group versus controls, and significantly downregulated in treatment group versus no-treatment group."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Hsa-miR-3184-3p, hsa-miR-24-3p, and hsa-miR-197-3p were validated to be remarkably upregulated in no-treatment group versus controls, and significantly downregulated in treatment group versus no-treatment group.", "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:34938191"], "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:GSE160310"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE160310"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34938191", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2021.781276", "sha256": "sha256:3c5b68477f5aff92db822b381e2a02b07c6481fa18ede7fb51ccc5e52871d17f", "bytes": 48028, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2021.781276", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8685391", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE160310", "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=GSE160310", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE160310", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4871112", "GSM4871113", "GSM4871114", "GSM4871115", "GSM4871116", "GSM4871117", "GSM4871118", "GSM4871119", "GSM4871120", "GSM4871121", "GSM4871122", "GSM4871123", "GSM4871124", "GSM4871125", "GSM4871126", "GSM4871127", "GSM4871128", "GSM4871129", "GSM4871130", "GSM4871131", "GSM4871132", "GSM4871133", "GSM4871134", "GSM4871135", "GSM4871136", "GSM4871137", "GSM4871138", "GSM4871139", "GSM4871140", "GSM4871141", "GSM4871142", "GSM4871143", "GSM4871144", "GSM4871145", "GSM4871146", "GSM4871147", "GSM4871148", "GSM4871149", "GSM4871150", "GSM4871151", "GSM4871152", "GSM4871153", "GSM4871154", "GSM4871155", "GSM4871156", "GSM4871157", "GSM4871158", "GSM4871159", "GSM4871160", "GSM4871161", "GSM4871162", "GSM4871163", "GSM4871164", "GSM4871165", "GSM4871166", "GSM4871167", "GSM4871168", "GSM4871169", "GSM4871170", "GSM4871171", "GSM4871172", "GSM4871173", "GSM4871174", "GSM4871175", "GSM4871176", "GSM4871177", "GSM4871178", "GSM4871179", "GSM4871180", "GSM4871181", "GSM4871182", "GSM4871183", "GSM4871184", "GSM4871185", "GSM4871186", "GSM4871187", "GSM4871188", "GSM4871189", "GSM4871190", "GSM4871203", "GSM4871204", "GSM4871205", "GSM4871206", "GSM4871207", "GSM4871208", "GSM4871209", "GSM4871210", "GSM4871211", "GSM4871212", "GSM4871213", "GSM4871214", "GSM4871215", "GSM4871216", "GSM4871217", "GSM4871218", "GSM4871219", "GSM4871220", "GSM4871221", "GSM4871222", "GSM4871223", "GSM4871224", "GSM4871225", "GSM4871226", "GSM4871227", "GSM4871228", "GSM4871229", "GSM4871230", "GSM4871231", "GSM4871232", "GSM4871233", "GSM4871234", "GSM4871235", "GSM4871236", "GSM4871237", "GSM4871238", "GSM4871239", "GSM4871240", "GSM4871241", "GSM4871242", "GSM4871243", "GSM4871244", "GSM4871245", "GSM4871246", "GSM4871247", "GSM4871248", "GSM4871249", "GSM4871250", "GSM4871251", "GSM4871252", "GSM4871253", "GSM4871254", "GSM4871255", "GSM4871256", "GSM4871257", "GSM4871258", "GSM4871259", "GSM4871260", "GSM4871261", "GSM4871262", "GSM4871263", "GSM4871264", "GSM4871265", "GSM4871266", "GSM4871267", "GSM4871268", "GSM4871269", "GSM4871270", "GSM4871271", "GSM4871272", "GSM4871273", "GSM4871274", "GSM4871275", "GSM4871276", "GSM4871277", "GSM4871278", "GSM4871279", "GSM4871280", "GSM4871281"], "sample_count": 158, "group_sizes": null, "group_sizes_basis": null, "platform": "20301", "taxon": "Homo sapiens", "title": "In-depth transcriptomic analyses investigating molecular mechanisms underlying diabetic retinopathy", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE160310 not downloaded", "asset:data:geo:GSE160310 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student t-test"}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-4", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "χ2"}}, {"id": "method-5", "family": null, "specific": null, "label": "DEGseq", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differentially expressed miRNAs (DEMIs) were analyzed by DEGseq, 8 and only the genes (miRNAs) with the absolute value of Log2Ratio ≥1 and Q value ≤0.01 were considered as DEMIs (Wang, Feng et al., 2010)."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE160310"], "resolved_accessions": ["GSE160310"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE160310 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:34938191", "data:geo:GSE160310"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE160310"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:12:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14612, "completion_tokens": 1158, "cached_tokens": 0}}, "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:34938191", "type": "paper", "label": "pmid:34938191"}, {"id": "source:pmid:34938191", "type": "manuscript", "label": "PMID 34938191 full text"}, {"id": "data:geo:GSE160310", "type": "dataset", "label": "GEO GSE160310"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34938191", "type": "paper", "label": "pmid:34938191"}, {"id": "source:pmid:34938191", "type": "manuscript", "label": "PMID 34938191 full text"}, {"id": "data:geo:GSE160310", "type": "dataset", "label": "GEO GSE160310"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34938191", "type": "extraction", "used": ["source:pmid:34938191"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE160310", "type": "accession_resolution", "used": ["data:geo:GSE160310"], "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:34938191", "parent_hash": "sha256:e39d71aaeb093ab9fd27810d87e37bd65ea43ed4611426da826b9215638bf505", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE160310 licence not read", "asset:data:geo:GSE160310 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "amplicon_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ve Diabetic Retinopathy Patients Detected by Next-Generation Sequencing.", "ercept injection (treatment group). Methods: Next-generation sequencing was performed to determine the miRNA profile"], "order_basis": "paper_text_order:71", "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": 0.93, "evidence": ["ated miRNAs were validated with quantitative real-time PCR (qRT-PCR) in another cohort. The mRNA profil"], "order_basis": "paper_text_order:702", "id": "assay:2"}, {"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": ["Student t-test"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}