Multi-omics characterization of RNF157 expression patterns in hepatocellular carcinoma and development of an RNF157-associated prognostic signature

TL;DR

This study explores RNF157 expression in liver cancer using multi-omics and single-cell data to develop a prognostic model linked to the tumor microenvironment.

Contribution

The study introduces a novel RNF157-associated prognostic signature for hepatocellular carcinoma based on single-cell and multi-omics analysis.

Findings

RNF157 shows heterogeneous expression in cancer-associated fibroblasts and tumor-associated macrophages.

The prognostic model achieved moderate predictive performance with AUC values between 0.65 and 0.78.

Gene depletion experiments reduced specific TME cell populations, confirming experimental manipulation success.

Abstract

Hepatocellular carcinoma (HCC) remains a highly lethal malignancy due to tumor heterogeneity and treatment resistance. This study characterized E3 ubiquitin ligase RNF157 expression patterns in HCC through integrated multi-omics and single-cell analysis, developed an RNF157-associated prognostic signature, and explored its relationship with tumor microenvironment (TME) populations.

Clinical and RNA expression data were obtained from TCGA, GEO databases, and scRNA-seq datasets (GSE149614). Protein-protein interaction networks were constructed via STRING database. Based on single-cell analysis revealing RNF157’s heterogeneous expression in cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), we performed validation experiments using lentiviral shRNAs targeting FAP in CAFs and CD11b in TAMs. All experiments included appropriate controls with three independent biological replicates.

Single-cell analysis identified significant heterogeneity in HCC samples, with RNF157 showing variable expression across cell types within the TME. The prognostic model demonstrated moderate predictive performance (AUC: 0.65–0.78 for 1–5 years survival). Flow cytometry confirmed successful experimental manipulation of TME populations, with reduced FAP + CAFs (45.54%→22.01%) and CD11b+ TAMs (35.03%→24.18%) following respective gene depletion.

We characterized RNF157 expression patterns in HCC at single-cell resolution and established a prognostic signature with moderate predictive performance requiring independent validation before clinical application.

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