The analysis of gene co-expression network and immune infiltration revealed biomarkers between triple-negative and non-triple negative breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39834541", "kind": "science-record", "revision": 3, "content_hash": "sha256:bfb8cabaa3ba7ba388612c4fb06cbb7e082ed959836d5470f6611124895a9812", "created_at": "2026-11-01T20:30:08Z", "updated_at": "2026-11-01T22:13:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The analysis of gene co-expression network and immune infiltration revealed biomarkers between triple-negative and non-triple negative breast cancer.", "doi": "10.3389/fgene.2024.1505011", "pmid": "39834541", "authors": ["Yao Yi", "Yu Zhong", "Lianhua Xie", "Shuxian Lu", "Yifeng Zhang"], "journal": "Frontiers in genetics", "year": 2024, "abstract": "Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease with a worse prognosis. Despite ongoing efforts, existing therapeutic approaches show limited success in improving early recurrence and survival outcomes for TNBC patients. Therefore, there is an urgent need to discover novel and targeted therapeutic strategies, particularly those focusing on the immune infiltrate in TNBC, to enhance diagnosis and prognosis for affected individuals.\nMethods: The gene co-expression network and gene ontology analyses were used to identify the differential modules and their functions based on the GEO dataset of GSE76275. The Weighted Gene Co-Expression Network Analysis (WGCNA) was used to describe the correlation patterns among genes across multiple samples. Subsequently, we identified key genes in TNBC by assessing genes with an absolute correlation coefficient greater than 0.80 within the eigengene of the enriched module that were significantly associated with breast cancer subtypes. The diagnostic potential of these key genes was evaluated using receiver operating characteristic (ROC) curve analysis with three-fold cross-validation. Furthermore, to gain insights into the prognostic implications of these key genes, we performed relapse-free survival (RFS) analysis using the Kaplan-Meier plotter online tool. CIBERSORT analysis was used to characterize the composition of immune cells within complex tissues based on gene expression data, typically derived from bulk RNA sequencing or microarray datasets. Therefore, we explored the immune microenvironment differences between TNBC and non-TNBC by leveraging the CIBERSORT algorithm. This enabled us to estimate the immune cell compositions in the breast cancer tissue of the two subtypes. Lastly, we identified key transcription factors involved in macrophage infiltration and polarization in breast cancer using transcription factor enrichment analysis integrated with orthogonal omics.\nResults: The gene co-expression network and gene ontology analyses revealed 19 modules identified using the dataset GSE76275. Of these, modules 5, 11, and 12 showed significant differences between in breast cancer tissue between TNBC and non-TNBC. Notably, module 11 showed significant enrichment in the WNT signaling pathway, while module 12 demonstrated enrichment in lipid/fatty acid metabolism pathways. Subsequently, we identified SHC4/KCNK5 and ABCC11/ABCA12 as key genes in module 11 and module 12, respectively. These key genes proved to be crucial in accurately distinguishing between TNBC and non-TNBC, as evidenced by the promising average AUC value of 0.963 obtained from the logistic regression model based on their combinations. Furthermore, we found compelling evidence indicating the prognostic significance of three key genes, KCNK5, ABCC11, and ABCA12, in TNBC. Finally, we also identified the immune cell compositions in breast cancer tissue between TNBC and non-TNBC. Our findings revealed a notable increase in M0 and M1 macrophages in TNBC compared to non-TNBC, while M2 macrophages exhibited a significant reduction in TNBC. Particularly intriguing discovery emerged with respect to the transcription factor FOXM1, which demonstrated a significant regulatory role in genes positively correlated with the proportions of M0 and M1 macrophages, while displaying a negative correlation with the proportion of M2 macrophages in breast cancer tissue.\nConclusion: Our research provides new insight into the biomarkers and immune infiltration of TNBC, which could be useful for clinical diagnosis of TNBC.", "claims": [{"id": "claim-method", "statement": "To identify the different immune cell compositions of breast cancer tissue between TNBC and non-TNBC, we employed the CIBERSORT algorithm, using the leukocyte signature matrix (LM22) as the reference gene expression signatures (Newman et al., 2015).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39834541", "locator": "sections[5] \"Evaluation of immune cells between TNBC and Non-TNBC\" paragraph 2", "quote": "To identify the different immune cell compositions of breast cancer tissue between TNBC and non-TNBC, we employed the CIBERSORT algorithm, using the leukocyte signature matrix (LM22) as the reference gene expression signatures (Newman et al., 2015)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39834541", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CIBERSORT analysis showed that TNBC tissue had higher average proportions of M0 macrophages (20.5%) and M1 macrophages (12.1%) and a lower average proportion of M2 macrophages (13.0%) than non-TNBC tissue, where the corresponding proportions were 15.9%, 9.79%, and 18.6%, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39834541", "locator": "sections[16] \"Identification of the immune cell compositions between TNBC and Non-TNBC\" paragraph 2", "quote": "On average, TNBC samples showed higher proportions of M0 macrophages (20.5%) and M1 macrophages (12.1%) compared to non-TNBC, where M0 and M1 macrophages averaged 15.9% and 9.79%, respectively. Conversely, the average proportion of M2 macrophages in TNBC (13.0%) was notably lower than in non-TNBC (18.6%)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CIBERSORT analysis showed that TNBC tissue had higher average proportions of M0 macrophages (20.5%) and M1 macrophages (12.1%) and a lower average proportion of M2 macrophages (13.0%) than non-TNBC tissue, where the corresponding proportions were 15.9%, 9.79%, and 18.6%, respectively.", "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:39834541"], "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:GSE76275"], "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:GSE76275"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39834541", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2024.1505011", "sha256": "sha256:29d7b2fc6f24e998076fc59021e673446892a231b5ba9325d9517fa0fcfeaa9e", "bytes": 45795, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2024.1505011", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11743633", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE76275", "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=GSE76275", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE76275", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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