Comprehensive characterization of β-alanine metabolism-related genes in HCC identified a novel prognostic signature...

Area of Science:

• Oncology
• Metabolic pathways
• Cancer genomics

Background:

• Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally.
• Metabolic reprogramming is key to HCC progression.
• The role of β-alanine metabolism-related genes (βAMRGs) in HCC is largely unknown.

Purpose of the Study:

• To comprehensively evaluate the function of βAMRGs in HCC.
• To explore the pan-cancer landscape of βAMRGs.
• To classify HCC patients based on βAMRG expression and analyze their prognosis and immune microenvironments.

Main Methods:

• Integrated analysis of pan-cancer gene expression, mutation, and methylation data.
• Single-cell RNA sequencing (scRNA-seq) to assess β-alanine metabolism in hepatocytes.
• Patient stratification into subtypes based on βAMRG scores.
• Development and validation of a prognostic panel and nomogram using βAMRGs.

Main Results:

• Hepatocytes show high β-alanine metabolism activity, which is further activated during hepatocarcinogenesis.
• Three HCC subtypes were identified, with the highest βAMRG score group exhibiting the best prognosis.
• Significant variations in immune microenvironment, metabolism, and cell death were observed among subtypes.
• EHHADH was identified as a protective gene in HCC, downregulated in tumors and correlated with prognosis.

Conclusions:

• β-alanine metabolism plays a significant, previously unrecognized role in HCC.
• βAMRGs offer potential as diagnostic and therapeutic targets for liver cancer.
• The study provides novel insights into HCC pathophysiology and patient stratification.