A linkage between effectual genes in progression of CRC through canonical and non-canonical TGF-β signaling pathways

Different molecular signaling pathways have been involved in the incidence and progression of CRC. We aimed to examine the correlation between eight candidate genes, including TFG beta, SMAD2, SMAD4, RhoA, EGFR, MAP2K1, MTA1, and LEF1 in the progression of colorectal cancer (CRC) and their association with clinicopathological variables and CRC patients prognosis Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) analysis 2(-Delta Delta ct), were performed to assess the expression of eight genes in 64 and 122 patients with CRC, respectively and 20 normal samples were added for verification. We showed a positive correlation between SMAD2 and MAP2K1 (r = 0.337, P < 0.001), MAP2K1 and LEF1 (r = 0.187, P = 0.03), SMAD4 and RhoA (r = 0.214, P = 0.01) and as well, a negative correlation between SMAD2 and TGF beta (r = - 0.197, P = 0.02), and RhoA and LEF1 (r = - 0.180, P = 0.04) in tumor tissues. A decrease in RhoA mRNA expression was associated with the advanced TNM stage (P=0.01), while the EGFR and SMAD2 mRNA expression upregu-lated in advanced stages (P = 0.03, P = 0.03), respectively. Also, an increase in EGFR and SMAD4 protein expression was significantly associated with the advanced TNM stage (P=0.000) (P = .002), respectively. Perceiving the connections between canonical and non-canonical Transforming growth factor (TGF-beta) signaling pathway along with the epidermal growth factor receptor (EGFR) and WNT cascades may trigger the development of novel approaches for CRC prediction.

Automated summary

This study investigated the correlation between eight candidate genes and colorectal cancer (CRC) progression, as well as their association with clinicopathological variables and prognosis. The study found positive or negative correlations among several pairs of genes, and the expression levels of certain genes were associated with the TNM stage of the tumor.