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pmid:40603423

Exploring the molecular mechanisms of comorbidity between thyroid cancer and breast cancer through multi-omics data.

Rui Yang · Jiayi Li · Hongyang Zhang · Huan Liu · Bin Lian · Jinping Li

Scientific reports · 2025 doi:10.1038/s41598-025-06566-w

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title
Exploring the molecular mechanisms of comorbidity between thyroid cancer and breast cancer through multi-omics data.
doi
10.1038/s41598-025-06566-w
pmid
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Rui Yang
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Jiayi Li
[2]
Hongyang Zhang
[3]
Huan Liu
[4]
Bin Lian
[5]
Jinping Li
journal
Scientific reports
year
2025
abstract
Thyroid Cancer (TC) and Breast Cancer (BC) are highly prevalent malignancies in women, and studies have shown that they may be related by molecular mechanisms. However, the molecular regulatory networks and key genes involved in the co-occurrence of the two tumors are still unclear. This study aims to explore potential diagnostic markers and therapeutic targets using bioinformatics. The TC (GSE3467) and BC (GSE61304) datasets were downloaded from the NCBI GEO database, and the data were analyzed for differentially expressed genes (DEGs) using the limma package of the R language. Disease-related gene modules were screened by weighted gene co-expression network analysis (WGCNA), and the hub genes were further screened by computational ranking by semantic similarity. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the biological functions of hub genes. Immune infiltration analysis was performed to reveal the association and expression correlation between the hub genes and immune cells and to explore the relationship between the hub genes and genes related to immunity, autophagy, and ferroptosis. In addition, mRNA-miRNA regulatory networks were constructed, and key regulatory miRNAs were screened by network topology analysis. Potential therapeutic drugs were screened using online tools, and drug molecules were docked in parallel. A total of 58 overlapping differential genes associated with TC and BC were identified, 27 common genes were obtained by intersection with 133 common genes identified by WGCNA, and seven hub genes were obtained by screening. We found that hub genes in both diseases are associated with autophagy, and ferroptosis. Six key regulatory miRNAs were screened, and six potential therapeutic agents were identified using Enrichr and PubChem databases. This bioinformatics study elucidated the possible co-occurrence mechanisms of TC and BC, providing new insights into their underlying pathogenesis and exploring new targets for medical intervention.
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The gene expression matrix was processed using the limma package in R software (R version 4.4.1), and the gene expression data of the experimental and control groups were read and normalized to ensure comparability of expression levels between different samples.
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sections[7] "Identification of DEGs and functional enrichment analysis" paragraph 2
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The gene expression matrix was processed using the limma package in R software (R version 4.4.1), and the gene expression data of the experimental and control groups were read and normalized to ensure comparability of expression levels between different samples.
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Data availabilityThe datasets analyzed during the current study are available in the GEO repository at https://www.ncbi.nlm.nih.gov/geo/(accession number: GSE3467and GSE61304).
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sections[19] "WGCNA network construction and identification of hub genes" paragraph 4
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the top 7 genes were identified as hub genes (Fig.S1), ANGPTL1, FHL1, ID1, CD36, ID4, LIFR, and LYVE1 respectively, which were considered to potentially play a key regulatory role in the biological processes of TC and BC.
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further validate the gene expression trends, RT-qPCR analysis was first conducted (Fig.S5). The r
[1]
lidation at the mRNA and protein levels. (a) RT-qPCR results for ANGPTL1 and CD36 in TC. (b) RT-q
[2]
qPCR results for ANGPTL1 and CD36 in TC. (b) RT-qPCR results for ANGPTL1 and CD36 in BC. (c) West
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However, the molecular regulatory networks and key genes involved in the co-occurrence of the two tumors are still unclear. This study aims to explore potential diagnostic markers and therapeutic targets using bioinformatics. The TC (GSE3467) and BC (GSE61304) datasets were downloaded from the NCBI GEO database, and the data were analyzed for differentially expressed genes (DEGs) using the limma package of the R language. Disease-related gene modules were screened by weighted gene co-expression network analysis (WGCNA), and the hub genes were further screened by computational ranking by semantic similarity. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the biological functions of hub genes. Immune infiltration analysis was performed to reveal the association and expression correlation between the hub genes and immune cells and to explore the relationship between the hub genes and genes related to immunity, autophagy, and ferroptosis. In addition, mRNA-miRNA regulatory networks were constructed, and key regulatory miRNAs were screened by network topology analysis. Potential therapeutic drugs were screened using online tools, and drug molecules were docked in parallel. A total of 58 overlapping differential genes associated with TC and BC were identified, 27 common genes were obtained by intersection with 133 common genes identified by WGCNA, and seven hub genes were obtained by screening. We found that hub genes in both diseases are associated with autophagy, and ferroptosis. Six key regulatory miRNAs were screened, and six potential therapeutic agents were identified using Enrichr and PubChem databases. This bioinformatics study elucidated the possible co-occurrence mechanisms of TC and BC, providing new insights into their underlying pathogenesis and exploring new targets for medical intervention.", "claims": [{"id": "claim-method", "statement": "The gene expression matrix was processed using the limma package in R software (R version 4.4.1), and the gene expression data of the experimental and control groups were read and normalized to ensure comparability of expression levels between different samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40603423", "locator": "sections[7] \"Identification of DEGs and functional enrichment analysis\" paragraph 2", "quote": "The gene expression matrix was processed using the limma package in R software (R version 4.4.1), and the gene expression data of the experimental and control groups were read and normalized to ensure comparability of expression levels between different samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data availabilityThe datasets analyzed during the current study are available in the GEO repository at https://www.ncbi.nlm.nih.gov/geo/(accession number: GSE3467and GSE61304).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40603423", "locator": "sections[31] \"Data availability\" paragraph 2", "quote": "Data availabilityThe datasets analyzed during the current study are available in the GEO repository at https://www.ncbi.nlm.nih.gov/geo/(accession number: GSE3467and GSE61304)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Seven shared hub genes between thyroid cancer and breast cancer were identified: ANGPTL1, FHL1, ID1, CD36, ID4, LIFR, and LYVE1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40603423", "locator": "sections[19] \"WGCNA network construction and identification of hub genes\" paragraph 4", "quote": "the top 7 genes were identified as hub genes (Fig.S1), ANGPTL1, FHL1, ID1, CD36, ID4, LIFR, and LYVE1 respectively, which were considered to potentially play a key regulatory role in the biological processes of TC and BC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Seven shared hub genes between thyroid cancer and breast cancer were identified: ANGPTL1, FHL1, ID1, CD36, ID4, LIFR, and LYVE1.", "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:40603423"], "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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The r", "lidation at the mRNA and protein levels. (a) RT-qPCR results for ANGPTL1 and CD36 in TC. (b) RT-q", "qPCR results for ANGPTL1 and CD36 in TC. (b) RT-qPCR results for ANGPTL1 and CD36 in BC. (c) West", "ther validate the gene expression trends, RT-qPCR analysis was first conducted (Fig.S5). The r"], "order_basis": "paper_text_order:3356", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s. To confirm findings at the protein level, Western blotting was subsequently performed, which confirmed", "qPCR results for ANGPTL1 and CD36 in BC. (c) Western blotting results for ANGPTL1 and CD36 in TC. (d) West", "ting results for ANGPTL1 and CD36 in TC. (d) Western blotting results for ANGPTL1 and CD36 in BC. 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