Targeted Drug Screening Leveraging Senescence-Induced T-Cell Exhaustion Signatures in Hepatocellular Carcinoma

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) is a prevalent cancer with high mortality, often diagnosed at advanced stages.
• Limited early treatment options exist for HCC, necessitating novel diagnostic and therapeutic approaches.
• T-cell exhaustion, driven by cellular senescence, is implicated in HCC progression.

Purpose of the Study:

• To identify genes characteristic of T-cell exhaustion associated with senescence in HCC.
• To elucidate the interplay between senescence and T-cell exhaustion in HCC.
• To develop prognostic models and identify potential therapeutic targets for HCC.

Main Methods:

• Elastic net regression was used to construct prognostic models based on five signature genes (ENO1, STMN1, PRDX1, RAN, RANBP1).
• Gene expression analysis focused on the role of ENO1 in T-cell exhaustion and Treg infiltration in HCC.
• Molecular docking was employed to screen small molecule compounds targeting anti-tumor effects of exhaustion-related genes.

Main Results:

• A prognostic model was developed using five signature genes associated with T-cell exhaustion.
• Increased ENO1 expression in T cells correlates with T-cell exhaustion and Treg infiltration in HCC.
• Potential small molecule compounds were identified through molecular docking for therapeutic intervention.

Conclusions:

• The study identified key genes (ENO1, STMN1, PRDX1, RAN, RANBP1) linked to T-cell exhaustion and senescence in HCC.
• ENO1 emerges as a potential driver of T-cell exhaustion and Treg infiltration in HCC.
• Findings support the development of predictive biomarkers and novel therapeutic targets for HCC treatment.