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Expression and Interaction of OTU Deubiquitinases in Hepatocellular Carcinoma
Abstract
Deubiquitinases (DUBs) play crucial roles in cancer progression by regulating protein ubiquitination, yet their involvement in hepatocellular carcinoma (HCC) remains underexplored. This study investigates the expression and interactions of OTU (Ovarian Tumor) DUBs in HCC to evaluate their potential as diagnostic, prognostic, and therapeutic markers. Gene Expression Omnibus (GEO) microarray datasets were analyzed using GEO2R to compare gene expression profiles between HCC and normal liver tissues. Differentially expressed genes (DEGs) were identified based on stringent criteria of log fold change (logFC) > 2.0 and adjusted P-value < 0.05. The expression profiles of 16 OTU DUBs were examined, and a protein-protein interaction (PPI) network was constructed incorporating overlapping DEGs and selected OTU DUBs. Kaplan-Meier (KM) survival analysis was performed using patient data from The Cancer Genome Atlas (TCGA) to assess prognostic significance. The analysis identified OTULIN as the only OTU DUB meeting DEG criteria, showing significant downregulation. OTUB1, OTUB2, and OTUD6B exhibited near-threshold expression changes and were included for further analysis due to their potential relevance. The PPI network revealed OTUB1 and OTUB2 as integral components of the HCC interactome, connecting to key regulators such as FOXM1 and ERα, respectively. KM survival analysis demonstrated that high expression of OTUB1 and OTUB2 correlates with poorer overall survival, whereas OTULIN and OTUD6B showed no significant impact. These findings highlight the potential roles of OTUB1 and OTUB2 in modulating HCC-related pathways, positioning them as promising candidates for therapeutic exploration, despite their limitations as diagnostic or prognostic marker.
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