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Kahlert, C.* ; Lerbs, T.* ; Pecqueux, M.* ; Herpel, E.* ; Hoffmeister, M.* ; Jansen, L.* ; Brenner, H.* ; Chang-Claude, J.* ; Bläker, H.* ; Kloor, M.* ; Roth, W.* ; Pilarsky, C.* ; Rahbari, N.N.* ; Schölch, S.* ; Bork, U.* ; Reissfelder, C.* ; Weitz, J.* ; Aust, D.* ; Koch, M.*

Overexpression of SIX1 is an independent prognostic marker in stage I-III colorectal cancer.

Int. J. Cancer 137, 2104–2113 (2015)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Epithelial-to-mesenchymal transition (EMT) contributes significantly to tumor progression and metastasis. The assessment of EMT-associated transcription factors could be a promising approach to identify biomarkers and potential therapeutic targets in colorectal cancer. In our study, we focused on the transcription factor "Sine oculis homeobox" (SIX) 1, which is a member of the superfamily of the homeobox genes and has been described to promote EMT in different types of tumors. Immunohistochemistry against SIX1 was performed on colorectal mucosa, adenomas, carcinomas-in situ and primary adenocarcinomas. An expression score was developed and subsequently assessed for its prognostic value in two independent cohorts. Cohort 1 consisted of 128 patients with stage I-III colorectal cancer; cohort 2 included 817 patients with stage I-III colorectal cancer who had participated in the DACHS study. HCT-116 cells were transfected with SIX1 plasmids and subjected to migration and colony formation assays. The expression of SIX1 increases gradually from mucosa to colorectal adenocarcinomas (p > 0.0001). Univariate and multivariate analyses reveal that high expression of SIX1 is associated with decreased overall survival (cohort 1: HR: 4.01, CI: 1.20-14.07, p = 0.025; cohort 2: HR: 1.43, CI: 1.014-2.02, p = 0.047). Overexpression of SIX1 induces a more mesenchymal-like phenotype in HCT-116 cells and enhances tumor migration. High expression of SIX1 is an independent prognostic marker in colorectal cancer. It might be a promising biomarker to stratify patients into different risk groups. Moreover, targeting SIX1 might be a novel therapeutic approach in patients with colorectal cancer.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Emt ; Six1 ; Colorectal Cancer ; Prognosis
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Quellenangaben Band: 137, Heft: 9, Seiten: 2104–2113 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)