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A novel tumor-based epithelial-to-mesenchymal transition score that associates with prognosis and metastasis in patients with stage II/III colorectal cancer

Roseweir, A.K., Kong, C.Y., Park, J.H., Bennett, Lindsay, Powell, A.G.M.T., Quinn, J., van Wyk, H.C., Horgan, P.G., McMillan, D.C., Edwards, Joanne and Roxburgh, C.S. 2019. A novel tumor-based epithelial-to-mesenchymal transition score that associates with prognosis and metastasis in patients with stage II/III colorectal cancer. International Journal of Cancer 144 (18) , pp. 150-159. 10.1002/ijc.31739

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Abstract

It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial–mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15–3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17–6.86, p < 0.001) were associated with decreased cancer‐specific survival. The combined EMT score was also associated with increased tumor budding (p = 0.046), and systemic inflammation (p = 0.007), as well as decreased memory T‐cells within the stroma (p = 0.030) and at the invasive margin (p = 0.035). Furthermore, the combined EMT score was associated with cancer‐specific survival independent of TNM‐stage (HR 4.12 95% CI 2.30–7.39, p < 0.001). In conclusion, a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Wiley
ISSN: 0020-7136
Date of First Compliant Deposit: 26 July 2018
Date of Acceptance: 14 June 2018
Last Modified: 11 Jul 2019 02:05
URI: http://orca-mwe.cf.ac.uk/id/eprint/113466

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