| Sumario: | 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.
|
|---|