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

miR-143 and miR-145 have been reported as downregulated in colorectal cancer (CRC) compared to normal mucosa, with regulatory effects on proteins involved in carcinogenesis. These findings primarily derive from tissue homogenate analyses and experimental models. The present study employs in situ methodology to reassess miR-143 and miR-145 expression in CRC and their associations with validated protein targets within the native tumor microenvironment. Expression patterns of miR-143, miR-145, and eight previously experimentally validated target proteins were analyzed in clinical samples from 100 CRC patients using in situ hybridization, immunohistochemistry, and deep learning-based epithelial segmentation. Expression levels of miR-143 and miR-145 showed no significant difference between CRC and normal mucosa, though considerable inter-patient variability was observed. Among 11 examined miRNA-protein relationships, only four showed significant correlations, exhibiting positive associations that contrast with previously reported inverse relationships. Subgroup analyses revealed no statistically significant association between miRNA expression variability and examined clinicopathological parameters. These findings highlight the importance of in situ validation for results obtained from tissue homogenates and in vitro experiments. Additional research is warranted to determine the prognostic significance of miR-143 and miR-145 in clinical outcomes.