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pmid:33145306

Investigation of hub genes involved in diabetic nephropathy using biological informatics methods.

Zhanting Li · Jianxin Liu · Weiwei Wang · Yunchun Zhao · Dengfeng Yang · Xiaodong Geng

Annals of translational medicine · 2020 doi:10.21037/atm-20-5647

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33145306
kind
science-record
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sha256:3713bad2dac792de23a5f9a184a05f544b8fbe1de81a1e7ffbef13ce0d2965cf
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2026-11-01T15:41:14Z
updated_at
2026-11-01T22:02:27Z
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paper object · 10 fields
state
complete
title
Investigation of hub genes involved in diabetic nephropathy using biological informatics methods.
doi
10.21037/atm-20-5647
pmid
33145306
authors array · 6 items
[0]
Zhanting Li
[1]
Jianxin Liu
[2]
Weiwei Wang
[3]
Yunchun Zhao
[4]
Dengfeng Yang
[5]
Xiaodong Geng
journal
Annals of translational medicine
year
2020
abstract
BACKGROUND: The aim of this study was to find genes with significantly aberrant expression in diabetic nephropathy (DN) and determine their underlying mechanisms. METHODS: GSE30528 and GSE1009 were obtained by querying the Gene Expression Omnibus (GEO) database. The difference in target gene expression between normal renal tissues and kidney tissues in patients with DN was screened by using the GEO2R tool. Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, differentially expressed genes (DEGs) were analysed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then, the protein-protein interactions (PPIs) of DEGs were analyzed by Cytoscape with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes in this PPI network were recognized by centrality analysis. RESULTS: There were 110 genes with significant expression differences between normal and DN tissues. The differences in gene expression involved many functions and expression pathways, such as the formation of the extracellular matrix and the construction of the extracellular domain. The correlation analysis and subgroup analysis of 14 hub genes and the clinical characteristics of DN showed that CTGF, ALB, PDPN, FLT1, IGF1, WT1, GJA1, IGFBP2, FGF9, BMP2, FGF1, BMP7, VEGFA, and TGFBR3 may be involved in the progression of DN. CONCLUSIONS: We confirmed the differentially expressed hub genes and other genes which may be the novel biomarker and target candidates in DN.
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Pearson’s correlation analysis between hub genes, glomerular filtration rate (GFR), and proteinuria in patients with DN was performed using Nephroseq v5 online platform (http://v5.nephroseq.org). Comparisons between two groups were performed using an unpaired Student’s t-test.
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methodological
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null
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sections[7] "Statistical analysis" paragraph 2
quote
Pearson’s correlation analysis between hub genes, glomerular filtration rate (GFR), and proteinuria in patients with DN was performed using Nephroseq v5 online platform (http://v5.nephroseq.org). Comparisons between two groups were performed using an unpaired Student’s t-test.
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the published estimate and its evidence
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The GSE30528 microarray data package contained 22 samples of human glomerular tissue. The study samples were taken from healthy human transplant donors, diagnostic renal biopsies, and post-nephrectomy specimens. Further analysis of the specific composition showed that it included 9 DN kidney tissue samples and 13 control group kidney tissue samples.
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The GSE30528 microarray data package contained 22 samples of human glomerular tissue. The study samples were taken from healthy human transplant donors, diagnostic renal biopsies, and post-nephrectomy specimens. Further analysis of the specific composition showed that it included 9 DN kidney tissue samples and 13 control group kidney tissue samples.
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Homo sapiens
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Diabetic nephropathy
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The GSE30528 microarray data package contained 22 samples of human glomerular tissue. The study samples were taken from healthy human transplant donors, diagnostic renal biopsies, and post-nephrectomy specimens. Further analysis of the specific composition showed that it included 9 DN kidney tissue samples and 13 control group kidney tissue samples.
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The GSE30528 microarray data package contained 22 samples of human glomerular tissue. The study samples were taken from healthy human transplant donors, diagnostic renal biopsies, and post-nephrectomy specimens. Further analysis of the specific composition showed that it included 9 DN kidney tissue samples and 13 control group kidney tissue samples.
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GSM757009
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571
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Transcriptome Analysis of Human Diabetic Kidney Disease (DKD Glomeruli vs. Control Glomeruli)
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110 differentially expressed genes (DEGs) were identified from two profile datasets
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Identification of DEGs in DN
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Table 1
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110 differentially expressed genes (DEGs) were identified from two profile datasets
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Genes name
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Upregulated
[1]
ALOX5, FRY, CCL19, GRIK2, C1orf21, TAC1, CORO1A, IGLC1, THBS2, IL7R, UMOD, TDO2, TRBC1, IGK///IGKC
[2] array · 2 items
[0]
Downregulated
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PLCE1, MYO1B, IGF1, KLK6, SEPT11, COL4A5, CXADR, GJA1, CDC14A, PALLD, GRK5, GHR, EVI2A, FOXC1, MGAT5, PARVA, CDC42EP3, WT1-AS, FGF1, CHI3L1, CORO2B, NEBL, PLA2R1, COL4A3, NPHS1, WT1, TCF21, TRAM2, KCND3, ST3GAL6, TNNT2, BMP7, DUSP1, KBTBD11, GALC, GPRC5A, CD200, IGFBP2, MEGF9, BMP2, CLIC5, CAND2, HPGD, VEGFA, MME, TYRO3, AIF1SRGAP2C///SRGAP2B///SRGAP2, MIR6872///SEMA3B, CTGF, CMAHP, DPP6, PTGER4, CR1, PDPN, PRKAR2B, FLT1, PTPRD, NFASC, PTGDS, CTNNBIP1, KLK7, USP46, THSD7A, MAGI2, EXPH5, LOC101930416///LOC101929792///LOC100996724///PDE4DIP, FGF9, SPOCK2, PAMR1, DDN, APOD, F2R, HTRA1, CACNB2, NTNG1, PDE4B, CTDSPL, PTPRO, CDKN1C, GAS1, ZNF185, MAP1B, LOX, SULF1, MYL9, TGFBR3, LPL, F5, MCM6, SEMA5A, ALB, F3, ITGB5, DPYSL3, SPOCK1
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GO enrichment analysis of DEGs in DN
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DEG GO analysis in DN
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Table 2
caption
GO enrichment analysis of DEGs in DN
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Term
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3
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3.88E-02
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3.88E-02
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[3]
3.42E-02
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[3]
3.13E-02
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GO:0016525~negative regulation of angiogenesis
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3
[3]
3.13E-02
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[0]
GOTERM_BP_DIRECT
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GO:0070374~positive regulation of ERK1 and ERK2 cascade
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4
[3]
2.98E-02
[7] array · 4 items
[0]
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[2]
3
[3]
2.85E-02
[8] array · 4 items
[0]
GOTERM_BP_DIRECT
[1]
GO:0007217~tachykinin receptor signaling pathway
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2
[3]
2.75E-02
[9] array · 4 items
[0]
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[1]
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[2]
2
[3]
2.75E-02
[10] array · 4 items
[0]
GOTERM_BP_DIRECT
[1]
GO:0006919~activation of cysteine-type endopeptidase activity involved in apoptotic process
[2]
3
[3]
2.71E-02
[11] array · 4 items
[0]
GOTERM_BP_DIRECT
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4
[3]
2.52E-02
[12] array · 4 items
[0]
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3
[3]
2.44E-02
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GOTERM_BP_DIRECT
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4
[3]
2.25E-02
[14] array · 4 items
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2
[3]
2.07E-02
[15] array · 4 items
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1.82E-02
[16] array · 4 items
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4.44E-03
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5
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1.39E-03
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9.76E-04
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1.07E-02
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5
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1.11E-03
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[3]
3.73E-02
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2
[3]
3.08E-02
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[1]
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4
[3]
2.32E-02
[24] array · 4 items
[0]
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3
[3]
2.11E-02
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[0]
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[1]
GO:0005884~actin filament
[2]
3
[3]
1.59E-02
[26] array · 4 items
[0]
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[1]
GO:0005925~focal adhesion
[2]
7
[3]
7.97E-03
[27] array · 4 items
[0]
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[1]
GO:0005578~proteinaceous extracellular matrix
[2]
5
[3]
6.46E-03
[28] array · 4 items
[0]
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[1]
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8
[3]
5.65E-03
[29] array · 4 items
[0]
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[1]
GO:0070062~extracellular exosome
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28
[3]
4.23E-05
[30] array · 4 items
[0]
GOTERM_CC_DIRECT
[1]
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18
[3]
5.89E-07
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KEGG pathway enrichment analysis of DEGs in DN
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Signalling pathway enrichment analysis
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Table 3
caption
KEGG pathway enrichment analysis of DEGs in DN
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Gene symbol and full name of 14 hub genes in diabetic nephropathy
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PMC7575993
section_index
13
section_title
Association between the hub genes and clinical features of DN
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Table 4
caption
Gene symbol and full name of 14 hub genes in diabetic nephropathy
rows array · 15 items
[0] array · 2 items
[0]
Gene symbol
[1]
Full name
[1] array · 2 items
[0]
CTGF
[1]
Connective tissue growth factor
[2] array · 2 items
[0]
ALB
[1]
Albumin
[3] array · 2 items
[0]
PDPN
[1]
Podoplanin
[4] array · 2 items
[0]
FLT1
[1]
Fms-related tyrosine kinase 1
[5] array · 2 items
[0]
IGF1
[1]
Insulin-like growth factor 1
[6] array · 2 items
[0]
WT1
[1]
Wilms tumor 1
[7] array · 2 items
[0]
GJA1
[1]
Gap junction protein alpha 1
[8] array · 2 items
[0]
IGFBP2
[1]
Insulin-like growth factor binding protein 2
[9] array · 2 items
[0]
FGF9
[1]
Fibroblast growth factor 9
[10] array · 2 items
[0]
FGF1
[1]
Fibroblast growth factor 1
[11] array · 2 items
[0]
BMP2
[1]
Bone morphogenetic protein 2
[12] array · 2 items
[0]
BMP7
[1]
Bone morphogenetic protein 7
[13] array · 2 items
[0]
VEGFA
[1]
Vascular endothelial growth factor A
[14] array · 2 items
[0]
TGFBR3
[1]
Transforming growth factor beta receptor 3
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[1]
asset:data:geo:GSE1009 licence not read
[2]
asset:data:geo:GSE30528 not downloaded
[3]
asset:data:geo:GSE30528 licence not read
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[0]
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[1]
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[2]
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[0]
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[0]
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Pearson’s correlation analysis; unpaired Student’s t-test
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Pearson’s correlation analysis between hub genes, glomerular filtration rate (GFR), and proteinuria in patients with DN was performed using Nephroseq v5 online platform (http://v5.nephroseq.org). Comparisons between two groups were performed using an unpaired Student’s t-test.
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gaps array · 1 item
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capability object · 3 fields
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Automated Assays Laravel application and simulated adapters
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network.
capability object · 4 fields
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statements array · 1 item
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The GSE30528 microarray data package contained 22 samples of human glomerular tissue. The study samples were taken from healthy human transplant donors, diagnostic renal biopsies, and post-nephrectomy specimens. Further analysis of the specific composition showed that it included 9 DN kidney tissue samples and 13 control group kidney tissue samples.
basis
The paper names GSE30528, GSE1009 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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agent:corpus-assay-engine
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33145306", "kind": "science-record", "revision": 6, "content_hash": "sha256:3713bad2dac792de23a5f9a184a05f544b8fbe1de81a1e7ffbef13ce0d2965cf", "created_at": "2026-11-01T15:41:14Z", "updated_at": "2026-11-01T22:02:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Investigation of hub genes involved in diabetic nephropathy using biological informatics methods.", "doi": "10.21037/atm-20-5647", "pmid": "33145306", "authors": ["Zhanting Li", "Jianxin Liu", "Weiwei Wang", "Yunchun Zhao", "Dengfeng Yang", "Xiaodong Geng"], "journal": "Annals of translational medicine", "year": 2020, "abstract": "BACKGROUND: The aim of this study was to find genes with significantly aberrant expression in diabetic nephropathy (DN) and determine their underlying mechanisms.\nMETHODS: GSE30528 and GSE1009 were obtained by querying the Gene Expression Omnibus (GEO) database. The difference in target gene expression between normal renal tissues and kidney tissues in patients with DN was screened by using the GEO2R tool. Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, differentially expressed genes (DEGs) were analysed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then, the protein-protein interactions (PPIs) of DEGs were analyzed by Cytoscape with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes in this PPI network were recognized by centrality analysis.\nRESULTS: There were 110 genes with significant expression differences between normal and DN tissues. The differences in gene expression involved many functions and expression pathways, such as the formation of the extracellular matrix and the construction of the extracellular domain. The correlation analysis and subgroup analysis of 14 hub genes and the clinical characteristics of DN showed that CTGF, ALB, PDPN, FLT1, IGF1, WT1, GJA1, IGFBP2, FGF9, BMP2, FGF1, BMP7, VEGFA, and TGFBR3 may be involved in the progression of DN.\nCONCLUSIONS: We confirmed the differentially expressed hub genes and other genes which may be the novel biomarker and target candidates in DN.", "claims": [{"id": "claim-method", "statement": "Pearson’s correlation analysis between hub genes, glomerular filtration rate (GFR), and proteinuria in patients with DN was performed using Nephroseq v5 online platform (http://v5.nephroseq.org). 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Comparisons between two groups were performed using an unpaired Student’s t-test."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33145306"], "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:GSE1009"], "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:GSE1009"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33145306", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-20-5647", "sha256": "sha256:6114168cff361aa04f3b006e03870e7ffaca40ee80f30e879fea267b3d06a9df", "bytes": 29096, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/atm-20-5647", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7575993", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1009", "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=GSE1009", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1009", "version": null, "note": "The GSE30528 microarray data package contained 22 samples of human glomerular tissue. 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The study samples were taken from healthy human transplant donors, diagnostic renal biopsies, and post-nephrectomy specimens. Further analysis of the specific composition showed that it included 9 DN kidney tissue samples and 13 control group kidney tissue samples.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GSE30528 microarray data package contained 22 samples of human glomerular tissue. The study samples were taken from healthy human transplant donors, diagnostic renal biopsies, and post-nephrectomy specimens. Further analysis of the specific composition showed that it included 9 DN kidney tissue samples and 13 control group kidney tissue samples.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM756992", "GSM756993", "GSM756994", "GSM756995", "GSM756996", "GSM756997", "GSM756998", "GSM756999", "GSM757000", "GSM757001", "GSM757002", "GSM757003", "GSM757004", "GSM757005", "GSM757006", "GSM757007", "GSM757008", "GSM757009", "GSM757010", "GSM757011", "GSM757012", "GSM757013"], "sample_count": 22, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Transcriptome Analysis of Human Diabetic Kidney Disease (DKD Glomeruli vs. Control Glomeruli)", "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:33145306:1", "role": "table", "format": "jats-table", "media_type": 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"read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#t2", "version": null, "note": "GO enrichment analysis of DEGs in DN", "structure": {"pmcid": "PMC7575993", "section_index": 10, "section_title": "DEG GO analysis in DN", "row_count": 31, "column_count": 4}, "table": {"label": "Table 2", "caption": "GO enrichment analysis of DEGs in DN", "rows": [["Category", "Term", "Count", "P value"], ["GOTERM_BP_DIRECT", "GO:0030154~cell differentiation", "3", "3.88E-02"], ["GOTERM_BP_DIRECT", "GO:0014068~positive regulation of phosphatidylinositol 3-kinase signaling", "3", "3.88E-02"], ["GOTERM_BP_DIRECT", "GO:0006693~prostaglandin metabolic process", "2", "3.42E-02"], ["GOTERM_BP_DIRECT", "GO:0045669~positive regulation of osteoblast differentiation", "3", "3.13E-02"], ["GOTERM_BP_DIRECT", "GO:0016525~negative regulation of angiogenesis", "3", "3.13E-02"], ["GOTERM_BP_DIRECT", "GO:0070374~positive regulation of ERK1 and ERK2 cascade", "4", "2.98E-02"], 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