Abstract 3680: The expression profiles of activins and follistatin at the different stages of colorectal cancer

Background: Activins belong to the family of transforming growth factor-β and the mature proteins (activin-A, -B and AB) are formed by the dimerization of two β-subunits (βA & βB). The biological activities of activins are tightly regulated by their binding protein, follistatin. Activin-A is the most studied isoform in the biology of colorectal cancer (CRC) and none of the earlier studies explored the expression profiles of the other activins as well as follistatin. Objectives: This study measured the gene and protein expressions of activin βA- and βB-subunits together with follistatin in paired malignant and remote non-cancerous specimens that were obtained at the different stages of malignancy from patients diagnosed with primary sporadic CRC. Materials and methods: Archived paired cancerous and non-cancerous colonic specimens were obtained from a total of 30 patients diagnosed with primary CRC. Following the identification of cancer stages by expert histopathologists, the genes and proteins of the targeted molecules were measured by quantitative RT-PCR and immunohistochemistry, respectively. Results: The genes and proteins of both activin βA- and βB-subunits alongside follistatin were comparable between the non-cancerous specimens obtained at the different stages of cancer. Nevertheless, significant up-regulations in the genes and proteins of βA-subunit and follistatin simultaneously with a marked inhibition of the βB-subunit were detected in the malignant specimens compared with their counterpart non-malignant tissues. Additionally, the βA-subunit and follistatin showed substantial increases in the malignant sites as cancer progressed and the highest levels were detected in stage IV compared with the earlier stages. Opposingly, the βB-subunit decreased gradually and significantly with cancer advancement and the protein expression was completely lost at stage IV. Conclusions: This study suggests that the overexpression of activin βA-subunit and follistatin may contribute to colon carcinogenesis and tumor progression, whereas the βB-subunit could be associated with anti-tumorigenic activities. However, more studies are still needed to measure the levels of the activin mature proteins (e.g. activin-A, -B and -AB) together with follistatin to precisely characterize their roles in CRC tumorigenesis. Acknowledgment: This project was funded by the DEANSHIP OF SCIENTIFIC RESEARCH AT UMM AL-QURA UNIVERSITY; Project (17-MED-1-01-0068). Citation Format: Mohammed