Identification of Core Gene Biomarkers in Patients with Diabetic Cardiomyopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30662576", "kind": "science-record", "revision": 7, "content_hash": "sha256:d4f49ff5749dbd049b02aebe7f63cd1f234b08ee00e3ba257e22da2694d351dd", "created_at": "2026-11-01T15:40:40Z", "updated_at": "2026-11-01T22:00:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Core Gene Biomarkers in Patients with Diabetic Cardiomyopathy.", "doi": "10.1155/2018/6025061", "pmid": "30662576", "authors": ["Ning Li", "Haiming Wu", "Rongxin Geng", "Qizhu Tang"], "journal": "Disease markers", "year": 2018, "abstract": "Diabetic cardiomyopathy (DCM) is a disorder of the myocardium in diabetic patients, which is one of the critical complications of diabetes giving rise to an increased mortality. However, the underlying mechanisms of DCM remain incompletely understood presently. This study was designed to screen the potential molecules and pathways implicated with DCM. GSE26887 involving 5 control individuals and 7 DCM patients was selected from the GEO database to identify the differentially expressed genes (DEGs). DAVID was applied to perform gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was also constructed to visualize the interactions among these DEGs. To further validate significant genes and pathways, quantitative real-time PCR (qPCR) and Western blot were performed. A total of 236 DEGs were captured, including 134 upregulated and 102 downregulated genes. GO, KEGG, and the PPI network disclosed that inflammation, immune disorders, metabolic disturbance, and mitochondrial dysfunction were significantly enriched in the development of DCM. Notably, IL6 was an upregulated hub gene with the highest connectivity degree, suggesting that it may interact with a great many molecules and pathways. Meanwhile, SOCS3 was also one of the top 15 hub genes in the PPI network. Herein, we detected the protein level of STAT3 and SOCS3 in a mouse model with DCM. Western blot results showed that the protein level of SOCS3 was significantly lower while phosphorylated-STAT3 (P-STAT3) was activated in mice with DCM. In vitro results also uncovered the similar alterations of SOCS3 and P-STAT3 in cardiomyocytes and cardiac fibroblasts induced by high glucose (HG). However, overexpression of SOCS3 could significantly reverse HG-induced cardiomyocyte hypertrophy and collagen synthesis of cardiac fibroblasts. Taken together, our analysis unveiled potential biomarkers and molecular mechanisms in DCM, which could be helpful to the diagnosis and treatment of DCM.", "claims": [{"id": "claim-method", "statement": "The obtained data were presented as mean ± SD (standard deviation) and assessed by the two-tailed Student's t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30662576", "locator": "sections[11] \"2.9. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE26887"], "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:GSE26887"], "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:30662576", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2018/6025061", "sha256": "sha256:bd2a9386b529e4da3f7e150655046d6bc36d3ec1a7b82fa57301b5a20e9a7b5d", "bytes": 48350, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2018/6025061", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6313979", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE26887", "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=GSE26887", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE26887", "version": null, "note": "The data used to support the findings of this study are available from the corresponding author upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used to support the findings of this study are available from the corresponding author upon request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM662158", "GSM662159", "GSM662160", "GSM662161", "GSM662162", "GSM662163", "GSM662164", "GSM662165", "GSM662166", "GSM662167", "GSM662168", "GSM662169", "GSM662170", "GSM662171", "GSM662172", "GSM662173", "GSM662174", "GSM662175", "GSM662176", "GSM662177", "GSM662178", "GSM662179", "GSM662180", "GSM662181"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Transcriptome analysis of diabetic and non diabetic patients affected by post-ischemic heart failure", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:30662576:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b7b3b7e7e6bc4a67d966690d4956b67960db2c3c7df96773298171b4cbdbdc01", "bytes": 1200, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#tab1", "version": null, "note": "The top 5 upregulated and downregulated differentially expressed genes in patients with diabetic cardiomyopathy.", "structure": {"pmcid": "PMC6313979", "section_index": 13, "section_title": "3.1. Identification of DEGs", "row_count": 12, "column_count": 5}, "table": {"label": "Table 1", "caption": "The top 5 upregulated and downregulated differentially expressed genes in patients with diabetic cardiomyopathy.", "rows": [["DEGs", "Gene title", "Gene symbol", "LogFC", "Biological function"], ["Upregulated", "Natriuretic peptide A", "NPPA", "3.53", "Extracellular fluid volume and electrolyte homeostasis"], ["Secreted frizzled related protein 4", "SFRP4", "2.71", "Soluble modulators of Wnt signaling"], ["Desmocollin 1", "DSC1", "2.44", "Calcium-dependent glycoprotein"], ["Nebulin", "NEB", "2.4", "Cytoskeleton"], ["Frizzled-related protein", "FRZB", "2.36", "Soluble modulators of Wnt signaling"], [""], ["Downregulated", "Serpin family E member 1", "SERPINE1", "−2.48", "Inhibitor of fibrinolysis"], ["Serpin family A member 3", "SERPINA3", "−2.44", "Anti-inflammatory and antioxidant effects"], ["Ankyrin repeat domain 2", "ANKRD2", "−2.16", "Modulator of NF-κB-mediated inflammatory"], ["X-ray repair cross-complementing 4", "XRCC4", "−2.05", "DNA repair"], ["S100 calcium-binding protein A8", "S100A8", "−1.98", "Regulating inflammation and oxidative stress, activatingTLR4 signaling"]], "row_count": 12, "column_count": 5, "numeric_cells": 18, "header_rows": 1, "locator": "section[13]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:30662576:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d5cced7b3388f6a929678d58c2136b2b1972dfd9a7fd0f0a1f7ce75a164781cc", "bytes": 2378, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#tab2", "version": null, "note": "Gene ontology analysis of differentially expressed genes in patients with diabetic cardiomyopathy.", "structure": {"pmcid": "PMC6313979", "section_index": 14, "section_title": "3.2. GO Enrichment Analysis", "row_count": 32, "column_count": 5}, "table": {"label": "Table 2", "caption": "Gene ontology analysis of differentially expressed genes in patients with diabetic cardiomyopathy.", "rows": [["Expression", "Category", "Term", "Count", "%"], ["Upregulated", "GOTERM_BP_DIRECT", "GO:0035589~G-protein-coupled purinergic nucleotide receptor signaling pathway", "9", "0.05"], ["GOTERM_BP_DIRECT", "GO:0007155~fatty acid metabolism", "8", "0.05"], ["GOTERM_BP_DIRECT", "GO:0001501~mitochondrial membrane potential", "6", "0.04"], ["GOTERM_BP_DIRECT", "GO:0030198~extracellular matrix organization", "6", "0.04"], ["GOTERM_BP_DIRECT", "GO:0007409~mitochondrial permeability transition", "5", "0.03"], ["GOTERM_CC_DIRECT", "GO:0016021~integral component of membrane", "42", "0.25"], ["GOTERM_CC_DIRECT", "GO:0005886~plasma membrane", "37", "0.22"], ["GOTERM_CC_DIRECT", "GO:0070062~extracellular exosome", "29", "0.17"], ["GOTERM_CC_DIRECT", "GO:0005615~extracellular space", "22", "0.13"], ["GOTERM_CC_DIRECT", "GO:0005576~extracellular region", "20", "0.11"], ["GOTERM_MF_DIRECT", "GO:0008270~glucose transporter", "13", "0.08"], ["GOTERM_MF_DIRECT", "GO:0005509~calcium ion binding", "11", "0.07"], ["GOTERM_MF_DIRECT", "GO:0008201~heparin binding", "7", "0.05"], ["GOTERM_MF_DIRECT", "GO:0005518~collagen binding", "5", "0.03"], ["GOTERM_MF_DIRECT", "GO:0050661~NADP binding", "4", "0.03"], [""], ["Downregulated", "GOTERM_BP_DIRECT", "GO:0006954~inflammatory response", "11", "0.07"], ["GOTERM_BP_DIRECT", "GO:0008284~lipid intake", "9", "0.06"], ["GOTERM_BP_DIRECT", "GO:0042493~response to drug", "6", "0.04"], ["GOTERM_BP_DIRECT", "GO:0006955~immune response", "6", "0.04"], ["GOTERM_BP_DIRECT", "GO:0002576~platelet degranulation", "5", "0.04"], ["GOTERM_CC_DIRECT", "GO:0005886~plasma membrane", "31", "0.21"], ["GOTERM_CC_DIRECT", "GO:0005615~extracellular space", "23", "0.15"], ["GOTERM_CC_DIRECT", "GO:0005576~extracellular region", "21", "0.14"], ["GOTERM_CC_DIRECT", "GO:0070062~extracellular exosome", "21", "0.14"], ["GOTERM_CC_DIRECT", "GO:0005789~endoplasmic reticulum membrane", "13", "0.09"], ["GOTERM_MF_DIRECT", "GO:0005515~protein binding", "58", "0.39"], ["GOTERM_MF_DIRECT", "GO:0008083~mitochondrial uncoupling", "5", "0.03"], ["GOTERM_MF_DIRECT", "GO:0005125~cytokine activity", "5", "0.03"], ["GOTERM_MF_DIRECT", "GO:0003779~actin binding", "5", "0.03"], ["GOTERM_MF_DIRECT", "GO:0016791~phosphatase activity", "3", "0.03"]], "row_count": 32, "column_count": 5, "numeric_cells": 90, "header_rows": 1, "locator": "section[14]/table-wrap[1]#tab2"}}, {"id": "asset:table:pmid:30662576:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0995fc600241ffd45c1db0b7d886a430bbf814692b9ab91d60913406dfa1dcfb", "bytes": 915, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#tab3", "version": null, "note": "KEGG pathway analysis of differentially expressed genes in patients with diabetic cardiomyopathy.", "structure": {"pmcid": "PMC6313979", "section_index": 15, "section_title": "3.3. 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PPI Analysis", "row_count": 30, "column_count": 4}, "table": {"label": "Table 5", "caption": "Gene-specific primers used in quantitative real-time PCR.", "rows": [["Species", "Genes", "", "Sequences"], ["Mouse", "GAPDH", "Forward", "5′-ACTCCACTCACGGCAAATTC-3′"], ["Reverse", "5′-TCTCCATGGTGGTGAAGACA-3′"], [""], ["Mouse", "NPPA", "Forward", "5′-CCCTCCGATAGATCTGCCCT-3′"], ["Reverse", "5′-GTCAATCCTACCCCCGAAGC-3′"], [""], ["Mouse", "SFRP4", "Forward", "5′-AAAAGCCGTCCAGAGGAGTG-3′"], ["Reverse", "5′-GAGGGACTTGTGTTCGAGGG-3′"], [""], ["Mouse", "DSC31", "Forward", "5′-GATCAGGCCAGTGGAAATGT-3′"], ["Reverse", "5′-GTGTGTTTCGTGCAACCATC-3′"], [""], ["Mouse", "NEB", "Forward", "5′-ATCCTGTCCAAACTAAGGCTCG-3′"], ["Reverse", "5′-ACCTCTTTAGCATAGTAGTCCGC-3′"], [""], ["Mouse", "SERPINE1", "Forward", "5′-GGGTTCACTTTACCCCTCCG-3′"], ["Reverse", "5′-TAGGGCAGTTCCACAACGTC-3′"], [""], ["Mouse", "SERPINA3", "Forward", "5′-TGACCTTTCTCAGCACGACC-3′"], ["Reverse", "5′-AATAGGGGAGGATGGGAGCA-3′"], [""], ["Mouse", "ANKRD2", "Forward", "5′-TTGCCCAGGAGGAAGAGACT-3′"], ["Reverse", "5′-TGTCTCTCACGTTGGTGTCG-3′"], [""], ["Mouse", "XRCC4", "Forward", "5′-TTGGGCGCATCGGTTTATCT-3′"], ["Reverse", "5′-ACCAGTGCCTTTCTCAGCTC-3′"], [""], ["Mouse", "S100A8", "Forward", "5′-TTCGTGACAATGCCGTCTGA-3′"], ["Reverse", "5′-GGCCAGAAGCTCTGCTACTC-3′"]], "row_count": 30, "column_count": 4, "numeric_cells": 22, "header_rows": 1, "locator": "section[16]/table-wrap[2]#tab5"}}], "gaps": ["asset:data:geo:GSE26887 not downloaded", "asset:data:geo:GSE26887 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": 1.0, "band": "verbatim", "quote": "The obtained data were presented as mean ± SD (standard deviation) and assessed by the two-tailed Student's t-test."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "targets": [], "gaps": ["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. 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