# Single‐Cell RNA‐seq Reveals Deubiquitination Genes as Prognostic Markers in Hepatocellular Carcinoma

## TL;DR

This study uses single-cell RNA sequencing to identify deubiquitination genes as potential prognostic markers for liver cancer, offering a new tool for patient stratification.

## Contribution

The study introduces a 78-gene DUB-based risk signature for predicting hepatocellular carcinoma prognosis.

## Key findings

- DUB activity varies significantly between malignant and immune cells in HCC tumors.
- DUB-high cancer cells show increased inflammatory and IFN-γ signaling with immune infiltration.
- A 78-gene prognostic index effectively stratifies patient survival across multiple cohorts.

## Abstract

Hepatocellular carcinoma (HCC) carries a dismal prognosis, yet the contribution of deubiquitination—an essential posttranslational regulator—to its progression remains poorly defined.

Single‐cell RNA‐seq profiles of 13 treatment‐naïve HCC tumors were integrated with 374 TCGA and 243 ICGC bulk RNA‐seq cohorts. Deubiquitinase (DUB) activity was quantified per cell with AUCell; pathway enrichment was performed with clusterProfiler. A LASSO‐Cox machine learning pipeline was used to build a DUB‐based risk signature, which was cross‐validated internally and externally by time‐dependent ROC analysis.

Malignant cells exhibited divergent DUB transcription relative to immune compartments (myeloid, B). DUB‐high neoplastic subsets displayed heightened inflammatory and IFN‐γ signaling, concordant with brisk immune infiltration. A 78‐gene prognostic index robustly stratified survival in discovery and replication cohorts.

This study highlights the role of deubiquitination in HCC progression and its potential as a prognostic biomarker. The developed model could serve as a valuable tool for patient stratification and personalized treatment strategies, although further experimental validation is needed to confirm these findings.