A bioinformatic analysis found low expression and clinical significance of ATF4 in breast cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38312639", "kind": "science-record", "revision": 3, "content_hash": "sha256:0d1fd95181bc31d1b8b5b61f3d2483a8e628df255170db0845ce3df559c54efa", "created_at": "2026-11-01T19:20:15Z", "updated_at": "2026-11-01T22:11:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A bioinformatic analysis found low expression and clinical significance of ATF4 in breast cancer.", "doi": "10.1016/j.heliyon.2024.e24669", "pmid": "38312639", "authors": ["Lujing Shao", "Zhounan Zhu", "Xinyan Jia", "Yabin Ma", "Chunyan Dong"], "journal": "Heliyon", "year": 2024, "abstract": "Background: Activating Transcription Factor 4 (ATF4) expression exhibits differential patterns across different types of tumors. Besides, the pathogenesis of breast cancer is complex, and the exact relationship between ATF4 and ATF4 remains uncertain.\nMethods: The analysis of ATF4 expression was conducted by utilizing The Cancer Genome Atlas (TCGA) pan-cancer data, while the gene expression profile of breast cancer was checked by the comprehensive database-Gene Expression Omnibus database. In order to gain a more comprehensive understanding of the specific cell types that exhibit ATF4 expression within the microenvironment of breast cancer, we conducted a single-cell analysis of ATF4 using two distinct datasets of human breast cancer (GSE114717 and GSE11088, respectively). The spatial distribution of ATF4 within a tissue was demonstrated based on datasets obtained from the Human Protein Atlas (HPA) and SpatialDB. The clinical prognostic significance of ATF4 was assessed by analyzing clinical survival data obtained from TCGA, GSE4830, and GSE25055 datasets. We used the R package clusterProfiler to carry out an enrichment analysis of ATF4. We assessed how ATF4 impacts the growth and movement of breast cancer cell lines. We manipulated ATF4 levels using plasmid transfection techniques.\nResults: The expression of ATF4 was found to be suboptimal and demonstrated a significant correlation with enhanced disease-specific survival (p = 0.012) and overall survival (p = 0.032) in breast cancer as well as other malignancies. We conducted an analysis to investigate the interaction between the infiltration level of immune cells and the expression of ATF4, using samples obtained from TCGA with known immune cell infiltration scores. Furthermore, a notable positive correlation exists between the elevated expression of ATF4 and immune-related genomes, specifically those associated with chemokine as well as immunity. Subsequent examination revealed a notable augmentation in the cytodifferentiation of T cells into regulatory T (Treg) cells within tissues exhibiting elevated levels of ATF4 expression. ATF4 exhibits notable upregulation in the MDA-MB-231 cell, thereby exerting a substantial impact on cell proliferation and migration upon its knockdown. Conversely, the overexpression of ATF4 in the MCF7 Luminal A breast cancer cell line can also modulate cellular function.\nConclusions: Our study suggests that ATF4 helps T cells differentiate into Treg cells in breast cancer. ATF4 can represent a clinically useful biomarker to predict the overall survival rate, especially in patients with different subtypes of breast cancer. Provide certain guidance value for the development of targeted drugs or inhibitors targeting ATF4.", "claims": [{"id": "claim-method", "statement": "Association between ATF4 expression and breast cancer prognosis. (A) Kaplan–Meier analysis of OS, DSS and RFS in TCGA-BRCA. Results with logrank p < 0.05 are shown.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38312639", "locator": "sections[20] \"Correlation and enrichment analysis\" paragraph 3", "quote": "Association between ATF4 expression and breast cancer prognosis. (A) Kaplan–Meier analysis of OS, DSS and RFS in TCGA-BRCA. Results with logrank p < 0.05 are shown."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data associated with my study has not been deposited into a publicly available repository. The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38312639", "locator": "sections[30] \"Data availability statement\" paragraph 2", "quote": "Data associated with my study has not been deposited into a publicly available repository. 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We manipulated ATF4 levels using plasmid transfection techniques. Results: The expression of ATF4", "on cell proliferation and migration upon its knockdown. Conversely, the overexpression of ATF4 in t", "age in all cancers. Cell culture and plasmid transfection The cells utilized in this study were obtain", "oup for each repetition. The MCF7 cells were transfected with the plasmid OE-ATF4, whereas the MDA-MB"], "order_basis": "paper_text_order:1332", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["onversely, the overexpression of ATF4 in the MCF7 Luminal A breast cancer cell line can also m", "e (CO2) concentration. The MCF10a cells were cultured in a specialized culture medium. The cell cultu", "contamination. The 4T1, EMT6, MDA-MB-231 and MCF7 cell lines were cultivated in Dulbecco's Mod", "eplicates per group for each repetition. The MCF7 cells were transfected with the plasmid OE-A"], "order_basis": "paper_text_order:2370", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nisms Center located in Shanghai, China. The mice were cared for and utilized in accordance with a", "d with Tongji University in Shanghai, China. Mice were subcutaneous injected cell suspension (appro"], "order_basis": "paper_text_order:4245", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["om. Tumor tissues were collected for further flow cytometry. Statistical analysis The data are presented"], "order_basis": "paper_text_order:4792", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student's t-test"], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}