Label-free quantification of imaging features in the extracellular matrix of left and right-sided colon cancer...

Area of Science:

• Oncology
• Biophysics
• Materials Science

Background:

• Colorectal cancer (CRC) exhibits molecular and clinical heterogeneity between right-sided colon cancer (RSCC) and left-sided colon cancer (LSCC).
• While differences in genetics, proteomics, microbiota, and tumor microenvironment are studied, the extracellular matrix (ECM) collagen morphology in CRC remains underexplored.
• Collagen, a key ECM component, significantly influences tissue structure and cancer progression.

Purpose of the Study:

• To quantitatively analyze collagen fiber morphology and density in the ECM of human colon tumors using advanced imaging techniques.
• To investigate differences in collagen organization between healthy colon tissue, RSCC, and LSCC.
• To explore the potential of collagen fiber characteristics as biomarkers for CRC subclassification.

Main Methods:

• Employed 2-photon laser scanning microscopy (2PLSM) to capture intrinsic second-harmonic generation (SHG) signals from collagen fibers.
• Utilized texture analysis of SHG images to quantitatively assess collagen fiber organization and structural features.
• Compared collagen morphology in healthy colon tissue, RSCC, and LSCC samples.

Main Results:

• Significant differences in collagen fiber organization were observed between healthy and cancerous colon tissues.
• Tumor tissues showed a loss of collagen organization, with chaotic regions more prevalent in RSCC.
• LSCC samples exhibited a higher overall collagen content compared to RSCC and healthy tissues.

Conclusions:

• Collagen fiber morphology and density vary distinctly between RSCC and LSCC, offering a new perspective on CRC heterogeneity.
• Quantitative analysis of collagen structure via SHG imaging can differentiate tumor subtypes.
• These findings may contribute to improved CRC subclassification, therapeutic decision-making, and novel therapy design targeting ECM characteristics.