Bulk and Single-Cell Transcriptomes Reveal Exhausted Signature in Prognosis of Hepatocellular Carcinoma

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Hepatocellular carcinoma (HCC) is a heterogeneous cancer with poor outcomes.
• T cell exhaustion (TEX) contributes to immune evasion and treatment resistance in HCC.
• Understanding TEX is crucial for improving HCC patient prognosis.

Purpose of the Study:

• To characterize TEX-related transcriptional features in HCC.
• To integrate single-cell and bulk RNA sequencing data for comprehensive analysis.
• To identify a prognostic gene signature associated with TEX in HCC.

Main Methods:

• Calculated TEX scores using a 65-gene signature to classify samples into high-TEX and low-TEX groups.
• Identified differentially expressed genes from both scRNA-seq and bulk RNA-seq data.
• Developed a 26-gene prognostic signature using univariate Cox and LASSO regression.

Main Results:

• High-TEX group showed increased immune checkpoint and antigen presentation molecules.
• This suggests a more immunosuppressive yet potentially immunotherapy-responsive tumor microenvironment.
• Functional enrichment and PPI network analysis confirmed gene roles in immune regulation and tumor progression.

Conclusions:

• Provided a comprehensive characterization of the TEX landscape in HCC.
• Identified a robust 26-gene signature associated with prognosis and immune infiltration.
• Highlighted the potential of targeting TEX for personalized HCC immunotherapies.