High-resolution spatial multi-omics enables prognostic scoring in intrahepatic cholangiocarcinoma

Area of Science:

• Oncology
• Genomics
• Proteomics

Background:

• Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver cancer with poor outcomes.
• Current prognostic tools for iCCA are insufficient for precise risk stratification and treatment planning.
• Despite advances in targeted therapies and immunotherapy, effective management remains challenging.

Purpose of the Study:

• To develop and validate a novel spatial multi-modal scoring system for intrahepatic cholangiocarcinoma (iCCA) risk stratification.
• To integrate multi-omics data for a comprehensive understanding of the iCCA tumor microenvironment (TME).
• To provide a clinically translatable tool for guiding iCCA treatment decisions.

Main Methods:

• Comprehensive spatial multi-omics investigation using image mass cytometry (IMC), spatial proteomics, scRNA-seq, bulk proteomics, and mIF.
• Development of a spatial multi-modal scoring system based on micro-scale resolution (1mm²) analysis.
• Cross-scale validation of the scoring system in an independent cohort of 214 patients.

Main Results:

• A novel spatial multi-modal scoring system was developed and validated for iCCA.
• The scoring system effectively addresses intra- and intertumoral heterogeneity across different scales.
• Multi-omics characterization elucidated the biological basis of the scoring system's prognostic power.

Conclusions:

• The developed spatial multi-modal scoring system offers a promising tool for precise risk stratification in iCCA.
• This innovative framework provides insights into iCCA biology and TME.
• The system has the potential to guide therapeutic decisions and improve patient management in iCCA.