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pmid:39375405

Bioinformatics analysis of effective biomarkers and immune infiltration in type 2 diabetes with cognitive impairment and aging.

Qin Wang · Ye Yang

Scientific reports · 2024 doi:10.1038/s41598-024-74480-8

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Bioinformatics analysis of effective biomarkers and immune infiltration in type 2 diabetes with cognitive impairment and aging.
doi
10.1038/s41598-024-74480-8
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Qin Wang
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Ye Yang
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Scientific reports
year
2024
abstract
With the increasing prevalence of diabetes mellitus worldwide, type 2 diabetes mellitus (T2D) combined with cognitive impairment and aging has become one of the common and important complications of diabetes mellitus, which seriously affects the quality of life of the patients, and imposes a heavy burden on the patients' families and the society. Currently, there are no special measures for the treatment of cognitive impairment and aging in type 2 diabetes mellitus. Therefore, the search for potential biological markers of type 2 diabetes mellitus combined with cognitive impairment and aging is of great significance for future precisive treatment. We downloaded three gene expression datasets from the GEO database: GSE161355 (related to T2D with cognitive impairment and aging), GSE122063, and GSE5281 (related to Alzheimer's disease). Differentially expressed genes (DEGs) were identified, followed by gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was constructed using the STRING database, and the top 15 hub genes were identified using the CytoHubba plugin in Cytoscape. Core genes were ultimately determined using three machine learning methods: LASSO regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Linear Discriminant Analysis (LDA). The diagnostic performance of these genes was assessed using ROC curve analysis and validated in an independent dataset (GSE5281). Regulatory genes related to ferroptosis were screened from the FerrDb database, and their biological functions were further explored through GO and KEGG enrichment analyses. Finally, the CIBERSORT algorithm was used to analyze immune cell infiltration, and the correlation between core genes and immune cell infiltration levels was calculated, leading to the construction of an mRNA-miRNA regulatory network. In the GSE161355 and GSE122063 datasets, 217 common DEGs were identified. GSEA analysis revealed their enrichment in the PI3K-PLC-TRK signaling pathway, TP53 regulation of metabolic genes pathway, Notch signaling pathway, among others. PPI network analysis identified 15 candidate core genes, and further selection using LASSO, LDA, and SVM-RFE machine learning algorithms resulted in 6 core genes: BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1. ROC curve analysis indicated that these genes had good diagnostic performance in the GSE161355 dataset, with TP53 and IL1B achieving an AUC of 0.9, indicating the highest predictive accuracy. BCL6, HSP90AA1, CRYAB, and DNAJB1 also had AUCs greater than 0.8, demonstrating moderate predictive accuracy. Validation in the independent dataset GSE5281 showed that these core genes also had good diagnostic performance in Alzheimer's disease samples (AUC > 0.6). Ferroptosis-related analysis revealed that IL1B and TP53 play significant roles in apoptosis and immune response. Immune cell infiltration analysis showed that IL1B is significantly positively correlated with infiltration levels of monocytes and NK cells, while TP53 is significantly negatively correlated with infiltration levels of follicular helper T cells. The construction of the miRNA-mRNA regulatory network suggested that miR-150a-5p might play a key role in the regulation of T2D-associated cognitive impairment and aging by TP53. This study, by integrating bioinformatics and machine learning methods, identified BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1 as potential diagnostic biomarkers for T2D with cognitive impairment and aging, with a particular emphasis on the significance of TP53 and IL1B in immune cell infiltration. These findings not only enhance our understanding of the molecular mechanisms linking type 2 diabetes to cognitive impairment and aging, providing new targets for early diagnosis and treatment, but also offer new directions and targets for basic research.
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The samples in GSE161355 and GSE122063 were extracted and analysed using the limma package [3.52.2], respectively, to obtain DEGs of cases with type 2 diabetes combined with cognitive impairment and aging versus cases without diabetes combined with cognitive impairment and aging in the GSE161355 dataset; the same method was used to obtain DEGs of cases with AD and non-AD in the GSE122063 dataset DEGs of AD and non-AD patients in the dataset and de-emphasise the above 2 sets of results18. FDR was used to correct the q-value for multiple hypothesis testing, |log2FC| > 1 and P < 0.05 was statistically significant.
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The samples in GSE161355 and GSE122063 were extracted and analysed using the limma package [3.52.2], respectively, to obtain DEGs of cases with type 2 diabetes combined with cognitive impairment and aging versus cases without diabetes combined with cognitive impairment and aging in the GSE161355 dataset; the same method was used to obtain DEGs of cases with AD and non-AD in the GSE122063 dataset DEGs of AD and non-AD patients in the dataset and de-emphasise the above 2 sets of results18. FDR was used to correct the q-value for multiple hypothesis testing, |log2FC| > 1 and P < 0.05 was statistically significant.
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The sequencing data used to support the findings of this study have been deposited in the GEO repository (GSE161355, GSE122063 and GSE5281). The datasets generated and/or analysed during the current study are available in the NCBI repository, and the data used to support the findings of this study have been deposited in the GEO repository (GSE161355, GSE122063 and GSE5281). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161355https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122063https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5281.
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The sequencing data used to support the findings of this study have been deposited in the GEO repository (GSE161355, GSE122063 and GSE5281). The datasets generated and/or analysed during the current study are available in the NCBI repository, and the data used to support the findings of this study have been deposited in the GEO repository (GSE161355, GSE122063 and GSE5281). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161355https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122063https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5281.
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Six genes—BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1—were identified as potential diagnostic biomarkers for T2DM with cognitive impairment and aging.
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This study, by integrating bioinformatics and machine learning methods, identified BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1 as potential diagnostic biomarkers for T2D with cognitive impairment and aging, with a particular emphasis on the significance of TP53 and IL1B in immune cell infiltration.
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Six genes—BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1—were identified as potential diagnostic biomarkers for T2DM with cognitive impairment and aging.
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Dementia Comparison: VaD vs. AD vs. Controls
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GSM238963
sample_count
161
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570
taxon
Homo sapiens
title
Alzheimer's disease and the normal aged brain (steph-affy-human-433773)
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2026-11-01T15:39:54Z
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identifier_resolution_only_no_download_no_licence_read
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The samples in GSE161355 and GSE122063 were extracted and analysed using the limma package [3.52.2], respectively, to obtain DEGs of cases with type 2 diabetes combined with cognitive impairment and aging versus cases without diabetes combined with cognitive impairment and aging in the GSE161355 dataset; the same method was used to obtain DEGs of cases with AD and non-AD in the GSE122063 dataset DEGs of AD and non-AD patients in the dataset and de-emphasise the above 2 sets of results18. FDR was used to correct the q-value for multiple hypothesis testing, |log2FC| > 1 and P < 0.05 was statistically significant.
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The sequencing data used to support the findings of this study have been deposited in the GEO repository (GSE161355, GSE122063 and GSE5281). The datasets generated and/or analysed during the current study are available in the NCBI repository, and the data used to support the findings of this study have been deposited in the GEO repository (GSE161355, GSE122063 and GSE5281). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161355https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122063https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5281.
basis
The paper names GSE161355, GSE122063, GSE5281 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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that IL1B and TP53 play significant roles in apoptosis and immune response. Immune cell infiltratio
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The samples in GSE161355 and GSE122063 were extracted and analysed using the limma package [3.52.2], respectively, to obtain DEGs of cases with type 2 diabetes combined with cognitive impairment and aging versus cases without diabetes combined with cognitive impairment and aging in the GSE161355 dataset; the same method was used to obtain DEGs of cases with AD and non-AD in the GSE122063 dataset DEGs of AD and non-AD patients in the dataset and de-emphasise the above 2 sets of results18. FDR was used to correct the q-value for multiple hypothesis testing, |log2FC| > 1 and P < 0.05 was statistically significant.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39375405", "kind": "science-record", "revision": 4, "content_hash": "sha256:bdddc45131bae858a3c79ca428c08b4daea32a75fda6c65fb1bb4042e922baa7", "created_at": "2026-11-01T20:29:35Z", "updated_at": "2026-11-01T22:55:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics analysis of effective biomarkers and immune infiltration in type 2 diabetes with cognitive impairment and aging.", "doi": "10.1038/s41598-024-74480-8", "pmid": "39375405", "authors": ["Qin Wang", "Ye Yang"], "journal": "Scientific reports", "year": 2024, "abstract": "With the increasing prevalence of diabetes mellitus worldwide, type 2 diabetes mellitus (T2D) combined with cognitive impairment and aging has become one of the common and important complications of diabetes mellitus, which seriously affects the quality of life of the patients, and imposes a heavy burden on the patients' families and the society. Currently, there are no special measures for the treatment of cognitive impairment and aging in type 2 diabetes mellitus. Therefore, the search for potential biological markers of type 2 diabetes mellitus combined with cognitive impairment and aging is of great significance for future precisive treatment. We downloaded three gene expression datasets from the GEO database: GSE161355 (related to T2D with cognitive impairment and aging), GSE122063, and GSE5281 (related to Alzheimer's disease). Differentially expressed genes (DEGs) were identified, followed by gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was constructed using the STRING database, and the top 15 hub genes were identified using the CytoHubba plugin in Cytoscape. Core genes were ultimately determined using three machine learning methods: LASSO regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Linear Discriminant Analysis (LDA). The diagnostic performance of these genes was assessed using ROC curve analysis and validated in an independent dataset (GSE5281). Regulatory genes related to ferroptosis were screened from the FerrDb database, and their biological functions were further explored through GO and KEGG enrichment analyses. Finally, the CIBERSORT algorithm was used to analyze immune cell infiltration, and the correlation between core genes and immune cell infiltration levels was calculated, leading to the construction of an mRNA-miRNA regulatory network. In the GSE161355 and GSE122063 datasets, 217 common DEGs were identified. GSEA analysis revealed their enrichment in the PI3K-PLC-TRK signaling pathway, TP53 regulation of metabolic genes pathway, Notch signaling pathway, among others. PPI network analysis identified 15 candidate core genes, and further selection using LASSO, LDA, and SVM-RFE machine learning algorithms resulted in 6 core genes: BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1. ROC curve analysis indicated that these genes had good diagnostic performance in the GSE161355 dataset, with TP53 and IL1B achieving an AUC of 0.9, indicating the highest predictive accuracy. BCL6, HSP90AA1, CRYAB, and DNAJB1 also had AUCs greater than 0.8, demonstrating moderate predictive accuracy. Validation in the independent dataset GSE5281 showed that these core genes also had good diagnostic performance in Alzheimer's disease samples (AUC > 0.6). Ferroptosis-related analysis revealed that IL1B and TP53 play significant roles in apoptosis and immune response. Immune cell infiltration analysis showed that IL1B is significantly positively correlated with infiltration levels of monocytes and NK cells, while TP53 is significantly negatively correlated with infiltration levels of follicular helper T cells. The construction of the miRNA-mRNA regulatory network suggested that miR-150a-5p might play a key role in the regulation of T2D-associated cognitive impairment and aging by TP53. This study, by integrating bioinformatics and machine learning methods, identified BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1 as potential diagnostic biomarkers for T2D with cognitive impairment and aging, with a particular emphasis on the significance of TP53 and IL1B in immune cell infiltration. These findings not only enhance our understanding of the molecular mechanisms linking type 2 diabetes to cognitive impairment and aging, providing new targets for early diagnosis and treatment, but also offer new directions and targets for basic research.", "claims": [{"id": "claim-method", "statement": "The samples in GSE161355 and GSE122063 were extracted and analysed using the limma package [3.52.2], respectively, to obtain DEGs of cases with type 2 diabetes combined with cognitive impairment and aging versus cases without diabetes combined with cognitive impairment and aging in the GSE161355 dataset; the same method was used to obtain DEGs of cases with AD and non-AD in the GSE122063 dataset DEGs of AD and non-AD patients in the dataset and de-emphasise the above 2 sets of results18. 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The datasets generated and/or analysed during the current study are available in the NCBI repository, and the data used to support the findings of this study have been deposited in the GEO repository (GSE161355, GSE122063 and GSE5281). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161355https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122063https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5281."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Six genes—BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1—were identified as potential diagnostic biomarkers for T2DM with cognitive impairment and aging.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39375405", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "This study, by integrating bioinformatics and machine learning methods, identified BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1 as potential diagnostic biomarkers for T2D with cognitive impairment and aging, with a particular emphasis on the significance of TP53 and IL1B in immune cell infiltration."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Six genes—BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1—were identified as potential diagnostic biomarkers for T2DM with cognitive impairment and aging.", "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:39375405"], "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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