Integrative Mendelian Randomization and Multiomics Analysis Identifies CAF-Derived Complement Factor B as a...

Area of Science:

• Immunology
• Oncology
• Genetics

Background:

• Complement factor B (CFB) is involved in tumor inflammation, but its role in breast cancer is unclear.
• Investigating CFB's biological and clinical significance in breast cancer is crucial for understanding disease progression and treatment.

Purpose of the Study:

• To clarify the biological and clinical significance of CFB in breast cancer.
• To explore CFB as a potential prognostic and therapeutic biomarker.

Main Methods:

• Integrated genetic epidemiology, multiomics transcriptomics, and AI-driven drug prediction.
• Mendelian randomization, single-cell transcriptomics, and bioinformatics analyses were employed.

Main Results:

• CFB levels are causally associated with breast cancer risk.
• High CFB expression in cancer-associated fibroblasts (CAFs) correlates with advanced stage, metastasis, poor survival, and an immunosuppressive tumor microenvironment.
• CFB-high and CFB-mutated tumors show enhanced sensitivity to PARP inhibitors, with mechanistic links to DNA damage.

Conclusions:

• CFB is a genetically associated risk protein and a prognostic biomarker in breast cancer.
• CFB expression and mutations indicate potential therapeutic targets, especially for PARP inhibitor sensitivity.
• Findings support CFB-driven precision therapy for breast cancer.