Ubiquitin-Proteasome Axis, Especially Ubiquitin-Specific Protease-17 (

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• High-grade serous ovarian cancer (HGSOC) is characterized by complex genetic alterations.
• Understanding gene expression differences between primary tumors, metastatic sites, and circulating tumor cells is crucial for HGSOC progression.
• Ascites and peritoneal implants represent distinct microenvironments influencing tumor cell behavior.

Purpose of the Study:

• To compare gene expression profiles and functional pathways in primary HGSOC tumors, metastatic peritoneal implants, and malignant cells within ascites.
• To identify key molecular differences and similarities across these distinct tumor compartments.
• To explore the role of specific gene families, such as USP17, in HGSOC progression and metastasis.

Main Methods:

• Comparative analysis of messenger RNA (mRNA) expression profiles from tissue biopsies (primary tumor, peritoneal implant) and ascites fluid from 10 HGSOC patients.
• Utilized gene ontology and pathway analysis to functionally characterize differentially expressed genes.
• Focused on identifying common and unique gene expression patterns across the three sample types.

Main Results:

• Significant gene expression differences were observed: 5 genes between primary tumor and peritoneal implant, 979 between primary tumor and ascites, and 649 between peritoneal implant and ascites.
• Commonly enriched gene ontology functions included protein deubiquitination, ubiquitin-dependent protein catabolism, and apoptotic processes.
• Genes associated with these functions predominantly belonged to the USP17 gene family.

Conclusions:

• Malignant cells in ascites exhibit substantial genetic divergence from primary tumors, suggesting dynamic adaptation within the ascites environment.
• The significant overlap in functions like protein deubiquitination and apoptosis between ascites and peritoneal implants indicates shared regulatory mechanisms.
• USP17 family genes are implicated in epithelial-mesenchymal transition (EMT), positioning USP17 as a potential therapeutic target for HGSOC metastasis.