Integrin Beta 4 Protein Expression Bimodally Predicts Sensitivity to CDK4/6 Inhibition and Resistance to Immunotherapy in Breast Cancer.
Background: Integrin beta 4 (ITGB4) has been implicated in breast cancer progression, yet its clinical utility as a biomarker remains unclear due to inconsistent findings across studies. This discrepancy may stem from the failure to distinguish between RNA and protein levels. Methods: We performed a...
| Publicado en: | Breast Journal Vol. 2026; pp. 1 - 15 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
4/22/2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=193163690&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 193163690 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 1075122X ET6 jtl: Breast Journal issn: 1075122X maglogo: Y pubinfo: dt: 4/22/2026 vid: 2026 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 193163690 193163690 193163690 10.1155/tbj/7668096 193163690 ppf: 1 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Integrin Beta 4 Protein Expression Bimodally Predicts Sensitivity to CDK4/6 Inhibition and Resistance to Immunotherapy in Breast Cancer. aug: au: Zhu, Zhi-Min Hu, Lei Ma, Yan-Wen Zhu, Qiong-Ni Wesley, Hannah affil: Department of Pharmaceutics,, Shanghai Eighth People's Hospital,, Shanghai, China, sh8y.com sug: subj: Breast Neoplasms Drug Therapy Immunotherapy Antineoplastic Agents Therapeutic Use Antineoplastic Agents Pharmacodynamics Receptors, Cell Surface Drug Effects Tumor Markers, Biological Blood Predictive Value of Tests Sensitivity and Specificity Drug Resistance, Neoplasm Cyclin-Dependent Kinases Drug Effects Gene Expression Protein Kinase Inhibitors Therapeutic Use RNA Drug Effects Human Female Aged Cell Line, Tumor Drug Effects MicroRNA Drug Effects Breast Neoplasms Prognosis Disease Progression Multiomics Immunohistochemistry Microarray Analysis Breast Neoplasms Classification Confidence Intervals Intracellular Signaling Peptides and Proteins Drug Effects Receptors, Estrogen Drug Effects Individualized Medicine Predictive Validity Retrospective Design Record Review Prospective Studies Cell Proliferation Drug Effects Neoplasm Recurrence, Local Survival Analysis Pharmacogenetics Correlational Studies Proteomics Dose-Response Relationship, Drug Xenografts Neoadjuvant Therapy Cell Communication Drug Effects Dendritic Cells Drug Effects Neutrophils Drug Effects Immune Checkpoint Proteins Drug Effects Progression-Free Survival Overall Survival Phosphotransferases Drug Effects Extracellular Matrix Drug Effects Phenotype Funding Source Cell Culture Techniques Blotting, Western Multivariate Analysis Cox Proportional Hazards Model Descriptive Statistics Data Analysis Software T-Tests Mann-Whitney U Test Nonparametric Statistics Log-Rank Test Spearman's Rank Correlation Coefficient One-Way Analysis of Variance Post Hoc Analysis Aged: 65+ years Female ab: Background: Integrin beta 4 (ITGB4) has been implicated in breast cancer progression, yet its clinical utility as a biomarker remains unclear due to inconsistent findings across studies. This discrepancy may stem from the failure to distinguish between RNA and protein levels. Methods: We performed an integrated multiomics analysis of ITGB4 across breast cancer subtypes using data from TCGA, CPTAC, METABRIC, and GEO cohorts. Key findings were functionally validated using CDK4/6 inhibition in luminal cells and via immunohistochemistry on triple‐negative breast cancer (TNBC) tissue microarrays. Results: ITGB4 exhibited significant RNA–protein discordance across breast cancer subtypes. High ITGB4 protein expression predicted a favorable prognosis in ER‐positive breast cancer (HR = 0.58, 95% CI: 0.39–0.86, p = 0.007) and enhanced sensitivity to CDK4/6 inhibitors. Conversely, high ITGB4 expression in TNBC correlated with immunotherapy resistance, characterized by elevated PD‐L1/PD‐L2 expression and reduced cytotoxic lymphocyte infiltration. Mechanistically, we identified the ESR1/miR‐342‐5p/UBE2E3 axis as a potential regulator of ITGB4 protein stability. Conclusion: ITGB4 protein expression serves as a bimodal biomarker in breast cancer, predicting CDK4/6 inhibitor sensitivity in luminal subtypes while indicating immunotherapy resistance in TNBC. ITGB4 protein thus represents a critical biomarker for guiding personalized therapy in precision oncology. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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