• Somayeh Mohammadpour, Amir Torshizi Esfahani, Seyyedmohammadamin Khorasaniasl, Raana Karimpour, Farbod Bakhshian, Afshin Moradi, and Ehsan Nazemalhosseini-Mojarad.
• Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Tehran, Iran.
• Indian J Med Res. 2022 Jul 1; 156 (1): 646964-69.

Background & ObjectivesTransforming growth factor-beta (TGF-β) signalling pathway has been reported to be involved in metastasis and at the same time has been considered compellingly an important mediator of epithelial-to-mesenchymal transition (EMT). Besides, EMT process is maintained by zinc-finger E-box-binding homeobox 1 (ZEB1) gene which is induced by TGF-β pathway. TGF-β has been shown to be associated with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) phenomenon, which is one of the prognostic biomarkers of colorectal cancer (CRC). This study was conducted to determine the link among ZEB1-induced TGF-β, EMAST status and metastasis.MethodsThe expression level of ZEB1 was evaluated using quantitative reverse transcription (qRT) real-time PCR in 122 formalin fixed paraffin-embedded tissues of CRC sample with known EMAST status and TGF-β/Smad-dependent pathways. The association among ZEB1 expression, TGF-β signalling pathway, EMAST status and metastatic behaviour was examined.ResultsZEB1 gene expression level was higher in tumour tissues as compared to normal samples (P<0.045). In addition, ZEB1 positive expression level was associated significantly with metastasis (P=0.05), EMAST+ status (P=0.052) and activated TGF-β signalling pathway (P=0.002).Interpretation & ConclusionsOur results validated significant association between activated TGF-β signalling pathway and EMAST+ phenotype with higher expression of ZEB1 and higher level of metastasis.

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