Growing Human Hepatocellular Tumors Undergo a Global Metabolic Reprogramming

Area of Science:

• Oncology
• Metabolomics
• Proteomics

Background:

• Hepatocellular carcinoma (HCC) presents a significant clinical challenge due to poor prognosis, limited diagnostic tools, and high recurrence rates.
• Cancer cells, including those in HCC, must adapt their metabolism to survive and proliferate within the tumor microenvironment, especially under conditions of hypoxia and nutrient deprivation.
• Understanding these metabolic adaptations is crucial for developing effective diagnostic and therapeutic strategies for HCC.

Purpose of the Study:

• To investigate the global metabolic reprogramming in hepatocellular carcinoma (HCC) during tumor progression.
• To identify specific metabolic alterations and potential biomarkers associated with HCC development and recurrence.
• To develop a predictive model integrating metabolic data with clinical factors for assessing HCC recurrence risk.

Main Methods:

• Combined proteomics and metabolomics analysis of paired tumor and peritumoral tissues from 200 HCC patients.
• Differential analysis of proteins and metabolites involved in key metabolic pathways, including glycolysis, the tricarboxylic acid cycle, and pyrimidine synthesis.
• Integration of identified metabolite biomarkers with clinical and pathological data to build and validate a prognostic model.

Main Results:

• Significant liver-specific metabolic reprogramming and alterations were observed in HCC tissues, correlating with increasing tumor size.
• Differential regulation of proteins and metabolites in glycolysis, the tricarboxylic acid cycle, and pyrimidine synthesis was identified in serum, tumor, and peritumoral tissues.
• Several prognostic metabolite biomarkers associated with HCC metabolic reprogramming were identified and validated in a model predicting recurrence risk.

Conclusions:

• Hepatocellular carcinoma exhibits global metabolic reprogramming that changes with tumor growth and stage.
• Metabolomic alterations are linked to advanced disease stages and poorer clinical outcomes in HCC.
• Targeting cancer metabolism presents a promising therapeutic avenue for HCC treatment.