Elevated Serum FGG Levels Prognosticate and Promote the Disease Progression in Prostate Cancer

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Castration-resistant prostate cancer (CRPC) lacks effective treatments.
• Identifying novel biomarkers and therapeutic targets for CRPC is crucial.

Purpose of the Study:

• To investigate the role of fibrinogen gamma (FGG) as a potential biomarker and therapeutic target in CRPC.
• To explore the molecular mechanisms underlying FGG's function in CRPC.

Main Methods:

• Serum samples from CRPC and localized prostate cancer (PCa) patients analyzed using iTRAQ proteomics and ELISA.
• FGG expression in CRPC tissues and cells examined via immunohistochemistry, qPCR, and Western blot.
• Functional assays (proliferation, invasion, migration, apoptosis) performed after FGG knockdown in CRPC cells.
• In vivo studies using xenografts in a mouse model.
• Investigated FGG regulation by IL-6/STAT3 signaling pathway.

Main Results:

• Serum FGG levels were significantly higher in CRPC patients compared to PCa patients.
• FGG expression was upregulated in CRPC tissues and cells.
• FGG knockdown significantly reduced CRPC cell proliferation, invasion, and migration.
• FGG silencing induced significant apoptosis, upregulating p53, caspase 3, clea-caspase 3, and Bax, while downregulating Bcl2 and survivin.
• FGG knockdown in DU145 cells led to smaller xenografts.
• FGG expression is modulated by IL-6 via STAT3 phosphorylation in CRPC.

Conclusions:

• Fibrinogen gamma (FGG) is a potential prognostic marker for CRPC.
• FGG plays a significant role in CRPC progression.
• Targeting FGG may represent a novel therapeutic strategy for CRPC.