Integrated bioinformatics analyses identifying potential biomarkers for type 2 diabetes mellitus and breast cancer: In SIK1-ness and health.

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Identification of hub genes implicated in T2DM-BC molecular crosstalk may help elucidate on the causative mechanisms. For this, expression series GSE29231 (T2DM-adipose tissue), GSE70905 (BC- breast adenocarcinoma biopsies) and GSE150586 (diabetes and BC breast biopsies) were extracted from Gene Expression Omnibus (GEO) database, and analyzed to obtain differentially expressed genes (DEGs). The overlapping DEGs were determined using FunRich. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Transcription Factor (TF) analyses were performed on EnrichR software and a protein-protein interaction (PPI) network was constructed using STRING software. The network was analyzed on Cytoscape to determine hub genes and Kaplan-Meier plots were obtained. A total of 94 overlapping DEGs were identified between T2DM and BC samples. These DEGs were mainly enriched for GO terms RNA polymerase II core promoter proximal region sequence and its DNA binding, and cAMP response element binding protein, and KEGG pathways including bladder cancer, thyroid cancer and PI3K-AKT signaling. Eight hub genes were identified: interleukin 6 (IL6), tumor protein 53 (TP53), interleukin 8 (CXCL8), MYC, matrix metalloproteinase 9 (MMP9), beta-catenin 1 (CTNNB1), nitric oxide synthase 3 (NOS3) and interleukin 1 beta (IL1β). MMP9 and MYC associated unfavorably with overall survival (OS) in breast cancer patients, IL6, TP53, IL1β and CTNNB1 associated favorably, whereas NOS3 did not show any correlation with OS. Salt inducible kinase 1 (SIK1) was identified as a significant key DEG for comorbid samples when compared with BC, also dysregulated in T2DM and BC samples (adjusted p <0.05). Furthermore, four of the significant hub genes identified, including IL6, CXCL8, IL1B and MYC were also differentially expressed for comorbid samples, however at p < 0.05. Our study identifies key genes including SIK1, for comorbid state and 8 hub genes that may be implicated in T2DM-BC crosstalk. However, limitations associated with the insilico nature of this study necessitates for subsequent validation in wet lab. Hence, further investigation is crucial to study the molecular mechanisms of action underlying these genes to fully explore their potential as diagnostic and prognostic biomarkers and therapeutic targets for T2DM-BC association.", "claims": [{"id": "claim-method", "statement": "Each of the series were analyzed using the GEO2R tool on NCBI GEO website to obtain differentially expressed genes (DEGs) between diseased and normal/control samples (https://www.ncbi.nlm.nih.gov/geo/geo2r/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37556419", "locator": "sections[4] \"Differential gene expression analysis\" paragraph 2", "quote": "Each of the series were analyzed using the GEO2R tool on NCBI GEO website to obtain differentially expressed genes (DEGs) between diseased and normal/control samples (https://www.ncbi.nlm.nih.gov/geo/geo2r/)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available freely on the NCBI-GEO website; T2DM adipose tissue series GSE29231, breast adenocarcinoma series GSE70905 and diabetes and breast cancer series GSE150586.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37556419", "locator": "sections[22] \"Data Availability\" paragraph 2", "quote": "The datasets analysed during the current study are available freely on the NCBI-GEO website; T2DM adipose tissue series GSE29231, breast adenocarcinoma series GSE70905 and diabetes and breast cancer series GSE150586."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Eight hub genes were identified: interleukin 6 (IL6), tumor protein 53 (TP53), interleukin 8 (CXCL8), MYC, matrix metalloproteinase 9 (MMP9), beta-catenin 1 (CTNNB1), nitric oxide synthase 3 (NOS3) and interleukin 1 beta (IL1β).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37556419", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Eight hub genes were identified: interleukin 6 (IL6), tumor protein 53 (TP53), interleukin 8 (CXCL8), MYC, matrix metalloproteinase 9 (MMP9), beta-catenin 1 (CTNNB1), nitric oxide synthase 3 (NOS3) and interleukin 1 beta (IL1β)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Eight hub genes were identified: interleukin 6 (IL6), tumor protein 53 (TP53), interleukin 8 (CXCL8), MYC, matrix metalloproteinase 9 (MMP9), beta-catenin 1 (CTNNB1), nitric oxide synthase 3 (NOS3) and interleukin 1 beta (IL1β).", "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:37556419"], "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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