OTUD7B associates with immune infiltration and pharmacogenomic profiles in hepatocellular carcinoma: An integrative...

OTUD7B is a deubiquitinating enzyme involved in ubiquitin-mediated signaling; however, its clinical and biological relevance in hepatocellular carcinoma (HCC) remains incompletely understood. This study evaluated the expression, prognostic, functional, immune-related, and pharmacogenomic associations of OTUD7B through an integrative analysis of publicly available datasets.

OTUD7B mRNA expression was evaluated in TCGA-LIHC using UALCAN and independently examined in the GSE76427 microarray cohort. Protein expression was assessed using Clinical Proteomic Tumor Analysis Consortium and Human Protein Atlas data. Kaplan-Meier analyses were performed using GEPIA2. Multivariable Cox proportional hazards regression models were used to evaluate overall survival (OS) and disease-free survival (DFS) after adjustment for age, sex, pathological stage, histological grade, alcohol consumption, HBV status, and HCV status. Gene co-expression and functional enrichment analyses were conducted using LinkedOmics. Associations with immune-cell infiltration, immune-related genes, copy-number alterations, cancer-related pathways, and m6A regulators were examined using TIMER2.0 and GSCA. Pharmacogenomic associations between OTUD7B expression and drug sensitivity were evaluated using CTRP and GDSC datasets. Statistical significance was defined as p < 0.05, with false discovery rate correction applied where appropriate.

OTUD7B mRNA expression was significantly higher in TCGA-LIHC tumors than in normal liver tissues (p < 0.0001), and proteomic and immunohistochemical data supported increased protein expression. However, OTUD7B expression did not differ significantly between primary HCC and adjacent non-tumor tissues in GSE76427 (p = 0.393). High OTUD7B expression was associated with poorer OS in Kaplan-Meier analysis (HR = 1.6, p = 0.014), but this association did not remain significant after multivariable adjustment (adjusted HR = 1.14, 95% CI: 0.70-1.85, p = 0.597). No significant adjusted association was observed for DFS (adjusted HR = 1.09, 95% CI: 0.66-1.81, p = 0.740). OTUD7B expression was also correlated with m6A regulators, selected immune-related genes, computationally inferred immune-cell abundance, and pharmacogenomic drug-response profiles.

OTUD7B shows cohort-dependent expression and is associated with functional, immune-related, and pharmacogenomic features in HCC. However, its differential expression was not reproduced in GSE76427, and its prognostic association was not retained after multivariable adjustment. These hypothesis-generating findings require validation in independent clinical cohorts and experimental models.