UBTD1 Drives Ovarian Cancer Progression via Mutation-Associated Alterations, Stromal Microenvironment Remodeling, and...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Ubiquitin domain-containing protein 1 (UBTD1) plays roles in protein homeostasis and cell cycle regulation, with emerging implications in tumor biology.
• The specific function of UBTD1 in ovarian cancer (OC), a highly lethal malignancy characterized by late diagnosis, metastasis, and platinum resistance, remains largely unexplored.

Purpose of the Study:

• To investigate the role of UBTD1 in ovarian cancer (OC) by integrating multi-omics data and experimental validation.
• To elucidate the relationship between UBTD1 expression, genomic instability, tumor microenvironment, and clinical outcomes in OC.

Main Methods:

• Analysis of UBTD1 expression, prognosis, mutation features, and immune microenvironment using TCGA and GEO public databases.
• Single-cell RNA-seq analysis with Seurat, hdWGCNA, and CopyKAT to characterize UBTD1-associated cell states and copy number variation (CNV) burden.
• Functional assays including UBTD1 knockdown, RNA sequencing, and rescue experiments in OC cell lines (A2780, SK-OV-3).

Main Results:

• UBTD1-low OC tumors exhibited enriched genomic instability, higher inferred CNV burden, and increased tumor mutation burden.
• UBTD1-high OC tumors were associated with increased stromal scores and infiltration of macrophages and neutrophils.
• Experimentally, UBTD1 was upregulated in OC, linked to poor prognosis, and its knockdown inhibited malignant phenotypes, enhanced cisplatin sensitivity, and suppressed TNF/AP-1/FOS signaling.

Conclusions:

• UBTD1 expression serves as a biomarker defining distinct mutation and microenvironmental states in ovarian cancer.
• UBTD1 functionally promotes malignant phenotypes in OC, potentially via the TNF/AP-1/FOS signaling pathway.
• Targeting UBTD1 may offer therapeutic strategies for improving ovarian cancer treatment outcomes.