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Background Colorectal cancers are derived from intestinal polyps. Normally, alterations in cell adhesion genes expression cause deviation from the normal cell cycle, leading to cancer development, progression, and invasion. The present study aimed to investigate the elusive expression pattern of CDC42, TAGLN, and GSN genes in patients with high and low-risk polyp samples, and also colorectal cancer patients and their adjacent normal tissues.Materials and methods In upcoming study, 40 biopsy samples from Taleghani Hospital (Tehran, Iran) were collected, consisting of 20 colon polyps and 20 paired adjacent normal tissues. The expression of the nominated genes CDC42, TAGLN, and GSN was analyzed using quantitative polymerase chain reaction (Q-PCR) and relative quantification was determined using the 2-ΔΔCt method. ROC curve analysis was performed to compare high-risk and low-risk polyps for the investigated genes. The expression of adhesion molecule genes was also evaluated using TCGA data and the correlation between adhesion molecule gene expression and immunophenotype was analyzed. The role of mi-RNAs and lncRNAs in overexpression of adhesion molecule genes was studied. Lastly, GO and KEGG were performed to identify pathways related to adhesion molecule gene expression in healthy, normal adjacent, and COAD tissues.Results The results showed that the expression patterns of these genes were significantly elevated in high-risk adenomas compared to low-risk polyps and normal tissues and were associated with various clinicopathological characteristics. The estimated AUC for CDC42, TAGLN, and GSN were 0.87, 0.77, and 0.80, respectively. The study also analyzed COAD cancer patient data and found that the selected gene expression in cancer patients was significantly reduced compared to high-risk polyps and healthy tissues. Survival analysis showed that while the expression level of the GSN gene had no significant relationship with survival rate, the expression of CDC42 and TAGLN genes did have a meaningful relationship, but with opposite effects, suggesting the potential use of these genes as diagnostic or prognostic markers for colorectal cancer.Conclusion The present study's findings suggest that the expression pattern of CDC42, TAGLN, and GSN genes was significantly increased during the transformation of normal tissue to polyp lesions, indicating their potential as prognostic biomarkers for colorectal polyp development. Further