Integrative Proteogenomic Characterization of Left-Sided and Right-Sided Colorectal Cancer

Area of Science:

• Oncology
• Genomics
• Proteomics

Background:

• Colorectal cancer (CRC) exhibits heterogeneity based on tumor location (left-sided vs. right-sided).
• Tumor laterality influences embryonic origin, molecular profiles, and clinical behavior, affecting treatment responses.
• Existing research suggests laterality-driven differences in targeted therapy and immunotherapy efficacy.

Purpose of the Study:

• To conduct a comprehensive multi-omics characterization of left- and right-sided CRC.
• To elucidate the molecular distinctions and tumor microenvironment variations between CRC laterality subtypes.
• To identify potential therapeutic strategies tailored to CRC laterality.

Main Methods:

• Integrated proteogenomic analysis including whole-exome sequencing, proteomics, and phosphoproteomics.
• Comparative study of 80 pairs of tumor and matched normal adjacent colorectal tissues.
• Analysis focused on tumor laterality to identify distinct molecular and immunological features.

Main Results:

• Left-sided CRC pathogenesis is linked to chromosomal instability; right-sided CRC is associated with microsatellite instability.
• Left-sided CRC shows increased microvascular endothelial cell proliferation, while right-sided CRC exhibits enhanced M1 macrophage-mediated antigen presentation.
• Differential DNA damage repair systems observed, with lower microsatellite instability-high development in left-sided CRC, suggesting varied immunotherapy responses.

Conclusions:

• Significant molecular and tumor microenvironment heterogeneity exists between left- and right-sided CRC.
• Understanding these laterality-driven differences is crucial for optimizing treatment strategies.
• This study provides a foundation for personalized therapeutic approaches in colorectal cancer based on tumor location.