Spatial Proteomic Profiling of Colorectal Cancer Revealed Its Tumor Microenvironment Heterogeneity

Area of Science:

• Oncology
• Proteomics
• Cancer Research

Background:

• Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
• Current therapeutic strategies for CRC are limited, with surgery remaining the primary treatment.
• Understanding the molecular landscape of CRC is crucial for developing novel therapies.

Purpose of the Study:

• To construct a comprehensive, spatially resolved quantitative proteome atlas of colorectal cancer.
• To explore the functional proteomic landscape and identify cancer-associated proteins and dysregulated pathways.
• To provide a valuable resource for discovering potential biomarkers and therapeutic targets in CRC.

Main Methods:

• Integration of histopathological analysis, laser capture microdissection, and advanced proteomics.
• Spatial proteome profiling of 200 colorectal tissue samples using SISPROT technology and Orbitrap Exploris 240.
• Proteomic analysis of tumoral and adjacent epithelial cells across different CRC stages and locations.

Main Results:

• Identification of over 4000 proteins from small tissue sections (2 mm² × 10 μm).
• Discovery of a spectrum of cancer-associated proteins and dysregulated pathways in various CRC regions (colon and rectum).
• Bioinformatics analysis revealed functional proteins and cell-type signatures linked to different tumor regions.

Conclusions:

• The study presents a detailed spatial proteome landscape of colorectal cancer.
• Identified proteins and pathways offer insights into CRC heterogeneity and progression.
• This atlas serves as a critical resource for future biomarker and therapeutic target discovery in colorectal cancer.