Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets
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View abstract on PubMed
Summary
This summary is machine-generated.This study deciphers breast ductal carcinoma (BRDC) progression using multi-omics, revealing key molecular events like TP53 mutations driving early stages and immune evasion mechanisms in later phases. AKR1C1 emerges as a therapeutic target.
Area Of Science
- Oncology
- Genomics
- Proteomics
Background
- Understanding breast ductal carcinoma (BRDC) progression is crucial for developing targeted therapies.
- The temporal sequence of biological events in BRDC remains poorly defined.
- Multi-omics approaches offer a powerful tool to unravel complex disease pathways.
Purpose Of The Study
- To elucidate the linear, multi-step progression of BRDC using comprehensive proteogenomic analysis.
- To identify key molecular drivers and therapeutic targets at different stages of BRDC.
- To provide insights into potential therapeutic strategies for BRDC treatment.
Main Methods
- Comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases.
- Integration of multi-omics data to map molecular changes during BRDC progression.
- In vitro validation of identified therapeutic targets and inhibitors.
Main Results
- Identified a linear progression model for BRDC.
- TP53 mutation-associated ESR1 overexpression drives transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS).
- 6q21 amplification-associated NR3C1 overexpression facilitates immune evasion in pure DCIS.
- The TIAM1-AR-AKR1C1 axis promotes invasion and migration in DCIS adjacent to invasive cancer (DCIS_adjIDC).
- AKR1C1 identified as a potential therapeutic target, with aspirin and dydrogesterone showing inhibitory effects.
Conclusions
- Proteogenomic analysis provides a detailed map of BRDC progression.
- Specific molecular events and pathways are critical at different stages of BRDC.
- AKR1C1 represents a promising therapeutic target for BRDC, with potential for drug intervention.
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