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Updated: Apr 23, 2026

Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Integrin Beta 4 Protein Expression Bimodally Predicts Sensitivity to CDK4/6 Inhibition and Resistance to
Zhi-Min Zhu1, Lei Hu2, Yan-Wen Ma3
1Department of Pharmaceutics, Shanghai Eighth People's Hospital, Shanghai, China, sh8y.com.
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.
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