miR-143 and miR-145 in Colorectal Cancer: A Digital Pathology Approach on Expressions and Protein Correlations

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• MicroRNAs (miRNAs), specifically miR-143 and miR-145, are implicated in colorectal cancer (CRC) development.
• Previous studies suggest these miRNAs are downregulated in CRC and regulate key proteins involved in carcinogenesis, primarily using tissue homogenates and experimental models.

Purpose of the Study:

• To re-evaluate miR-143 and miR-145 expression and their target protein associations within the native colorectal cancer tumor microenvironment using in situ methods.
• To validate findings from tissue homogenate analyses and experimental models in a clinical context.

Main Methods:

• Analysis of miR-143, miR-145, and eight validated target proteins in 100 colorectal cancer patient samples.
• Utilized in situ hybridization, immunohistochemistry, and deep learning-based epithelial segmentation for expression analysis.
• Examined miRNA-protein relationships and associations with clinicopathological parameters.

Main Results:

• miR-143 and miR-145 expression levels showed no significant difference between colorectal cancer and normal mucosa, but displayed high inter-patient variability.
• Only four out of eleven examined miRNA-protein relationships demonstrated significant correlations, all showing positive associations, contradicting previously reported inverse relationships.
• No significant association was found between miRNA expression variability and clinicopathological parameters.

Conclusions:

• In situ validation is crucial for results derived from tissue homogenates and in vitro experiments.
• The role and prognostic significance of miR-143 and miR-145 in colorectal cancer require further investigation within the native tumor context.