The proteomic characterization of the peritumor microenvironment in human hepatocellular carcinoma

Area of Science:

• Oncology
• Proteomics
• Cancer Biology

Background:

• The tumor microenvironment (TME) is typically studied in tumor tissue, focusing on progression rather than occurrence, recurrence, or metastasis.
• The concept of the peritumor microenvironment (PME) was introduced to analyze proteomic changes in liver tissues surrounding hepatocellular carcinoma (HCC).

Purpose of the Study:

• To conduct a proteomic characterization of the PME in HCC to understand its distinct roles in tumor occurrence and progression.
• To identify potential therapeutic targets and diagnostic markers based on PME differences.

Main Methods:

• Proteomic profiling of peritumor liver tissues from HCC patients.
• Comparative analysis of proteome composition and function between PME for occurrence (PME-O) and PME for progression (PME-P).
• Validation of identified targets, such as Thymidine phosphorylase (TYMP), in an orthotopic HCC mouse model.

Main Results:

• The PME for occurrence (PME-O) and progression (PME-P) exhibit distinct proteomic compositions and functions, with minimal overlap in proteins.
• Immunity is central to PME-O, while inflammation, angiogenesis, and metabolism are critical in PME-P.
• Proteome profiling identified three distinct PME subtypes associated with different HCC features.
• Thymidine phosphorylase (TYMP) was validated as an effective antiangiogenic target in an HCC mouse model.

Conclusions:

• The processes of HCC occurrence and progression are substantially different, driven by distinct PME characteristics.
• Proteomic insights into the PME offer new avenues for advancing cancer biology, diagnostics, and therapeutics for HCC.
• Targeting PME components, like TYMP, presents a promising strategy for HCC treatment.