The crosstalk between metabolic reprogramming and epithelial-mesenchymal transition and their synergistic roles in distant metastasis in breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38875364", "kind": "science-record", "revision": 3, "content_hash": "sha256:7c1ce418221481e748bc51e122a6c873e6cfb3cb2776a9936460d2f803088ae4", "created_at": "2026-11-01T20:28:56Z", "updated_at": "2026-11-01T22:12:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The crosstalk between metabolic reprogramming and epithelial-mesenchymal transition and their synergistic roles in distant metastasis in breast cancer.", "doi": "10.1097/MD.0000000000038462", "pmid": "38875364", "authors": ["Liyan Yu", "Yongni Chen", "Yingyu Chen", "Kangwei Luo"], "journal": "Medicine", "year": 2024, "abstract": "BACKGROUND: Metabolic reprogramming (MR) and epithelial-mesenchymal transition (EMT) are crucial phenomena involved in the distant metastasis of breast cancer (BRCA). This study aims to assess the risk of distant metastasis in BRCA patients based on MR and EMT processes and investigate their underlying mechanisms.\nMETHODS: Gene sets related to EMT and MR were downloaded. MR-related genes (MRG) and EMT-related genes (ERG) were obtained. Principal Component Analysis method was used to define the EMT Potential Index (EPI) and MR Potential Index (MPI) to quantify the EMT and MR levels in each tumor tissue. A linear scoring model, the Metastasis Score, was derived using the union of MRGs and ERGs to evaluate the risk of distant metastasis/recurrence in BRCA. The Metastasis Score was then validated in multiple datasets. Additionally, our study explored the underlying mechanism of the Metastasis Score and its association with tumor immunity, focusing on HPRT1 gene expression in breast cancer tissues of transfer and untransferred groups using experimental methods.\nRESULTS: A total of 59 MRGs and 30 ERGs were identified in the present study. Stratifying the dataset based on EPI and MPI revealed significantly lower survival rates (P < .05) in the MPI_high and EPI_high groups. Kaplan-Meier analysis indicated the lowest survival rate in the EPI-high + MPI-high group. The Metastasis Score demonstrated its ability to distinguish prognoses in GSE2034, GSE17705, and TCGA-BRCA datasets. Additionally, differences in mutated genes were found between the high- and the low-Metastasis Score groups, displaying significant associations with immune cell infiltration and anti-tumor immune status. Notably, the 13 genes included in the Metastasis Score showed a strong association with prognosis and tumor immunity. Immunohistochemistry and western blot results revealed high expression of the HPRT1 gene in the transfer group.\nCONCLUSION: This study established the Metastasis Score as a reliable tool for evaluating the risk of distant metastasis/recurrence in BRCA patients. Additionally, we identified key genes involved in MR and EMT crosstalk, offering valuable insights into their roles in tumor immunity and other relevant aspects.", "claims": [{"id": "claim-method", "statement": "The GSE2034 dataset was used to identify MR and EMT genes associated with distant metastasis or recurrence through univariate Cox analysis, with distant metastasis/recurrence time as the target variable.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38875364", "locator": "sections[14] \"3.1. Identification of MRG and ERG related to distant metastasis or recurrence\" paragraph 2", "quote": "The GSE2034 dataset was used to identify MR and EMT genes associated with distant metastasis or recurrence through univariate Cox analysis, with distant metastasis/recurrence time as the target variable."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article [and its supplementary information files].Supplemental Digital Content is available for this article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38875364", "locator": "sections[27] \"(untitled)\" paragraph 1", "quote": "All data generated or analyzed during this study are included in this published article [and its supplementary information files].Supplemental Digital Content is available for this article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study established the Metastasis Score as a reliable tool for evaluating the risk of distant metastasis/recurrence in BRCA patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38875364", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study established the Metastasis Score as a reliable tool for evaluating the risk of distant metastasis/recurrence in BRCA patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "This study established the Metastasis Score as a reliable tool for evaluating the risk of distant metastasis/recurrence in BRCA patients.", "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:38875364"], "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:GSE176078"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE176078"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38875364", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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Immunohistochemistry and western blot results revealed high expre", "tal results of HPRT1 Based on the results of immunohistochemistry, we found that the HPRT1 staining of breast", "ognosis of BRCA patients to some extent. (A) Immunohistochemical results of breast cancer specimens in the tr", "cancer specimens in the transfer group. (B) Immunohistochemical results of breast cancer specimens in the un"], "order_basis": "paper_text_order:1925", "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": ["and tumor immunity. Immunohistochemistry and western blot results revealed high expression of the HPRT", "he transfer group (P < 0.001) (Fig. 8C). The Western blot results showed that the protein level of HPR", "transfer group and untransferred group. 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