FAM84B promotes prostate tumorigenesis through a network alteration

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Prostate cancer (PC) is a significant health concern.
• Understanding the molecular drivers of PC tumorigenesis and progression is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the role of Family with sequence similarity 84 member B (FAM84B) in prostate cancer development and progression.
• To identify molecular pathways and biomarkers associated with FAM84B-driven prostate cancer.

Main Methods:

• Constructed a FAM84B mutant (ΔHRASLS) and generated prostate cancer cell lines expressing FAM84B or its mutant.
• Assessed cell proliferation, invasion, and soft agar growth in vitro.
• Evaluated tumor growth and lung metastasis in mouse models.
• Performed RNA sequencing to analyze transcriptomic changes and identify enriched pathways.
• Developed and validated a gene signature for predicting PC recurrence.

Main Results:

• FAM84B expression enhanced prostate cancer cell invasion and soft agar growth, while the ΔHRASLS mutant did not.
• FAM84B significantly increased xenograft tumor growth and lung metastasis in mice.
• RNA sequencing revealed 4976 differentially expressed genes and 51 enriched pathways in FAM84B-expressing tumors.
• A novel 27-gene signature (SigFAM) derived from these genes robustly predicted prostate cancer recurrence and was an independent risk factor.

Conclusions:

• FAM84B promotes prostate tumorigenesis and progression.
• FAM84B exerts its effects through a complex molecular network.
• The SigFAM gene signature is a valuable predictor of prostate cancer recurrence.