Angiogenic Prognostic Signature for Stratification in Hepatocellular Carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Hepatocellular carcinoma (HCC) is a major cause of cancer mortality.
• Angiogenesis is critical for HCC progression, yet effective biomarkers are scarce.

Purpose of the Study:

• To develop and validate an angiogenesis-related gene (ARG) signature for prognostic prediction in HCC.
• To investigate the role of SPP1 in angiogenesis and its relationship with the tumor immune microenvironment and drug sensitivity.

Main Methods:

• Utilized TCGA and ICGC data to construct and validate a prognostic ARG signature using LASSO-Cox regression.
• Performed in vitro and in vivo functional experiments for SPP1, analyzed single-cell RNA-seq data, and assessed drug sensitivity.
• Investigated the impact of the signature on immune checkpoint expression, stromal activity, and sorafenib sensitivity.

Main Results:

• A four-gene ARG signature (APOH, SLCO2A1, SPP1, VTN) accurately stratified HCC patients into high- and low-risk groups with differential survival.
• The high-risk group exhibited increased immune checkpoint expression and stromal activity.
• SPP1 knockdown inhibited angiogenesis; high-risk patients showed reduced sorafenib sensitivity, with sorafenib affecting specific signature genes.

Conclusions:

• A validated ARG-based prognostic signature improves risk stratification for HCC patients.
• The signature reveals connections between angiogenesis, the immune microenvironment, and therapeutic response in HCC.