CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer

Saito,Seiya; Okabe,Hirohisa; Watanabe,Masayuki; Ishimoto,Takatsugu; Iwatsuki,Masaaki; Baba,Yoshifumi; Tanaka,Youhei; Kurashige,Junji; Miyamoto,Yuji; Baba,Hideo

doi:10.3892/or.2013.2273

CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer

Authors:
- Seiya Saito
- Hirohisa Okabe
- Masayuki Watanabe
- Takatsugu Ishimoto
- Masaaki Iwatsuki
- Yoshifumi Baba
- Youhei Tanaka
- Junji Kurashige
- Yuji Miyamoto
- Hideo Baba
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Affiliations: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Published online on: February 5, 2013 https://doi.org/10.3892/or.2013.2273
Pages: 1570-1578

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Abstract

CD44 standard isoform (CD44s) is a cancer stem cell marker in many tumors, and is one of the CD44 isoforms.CD44v6 has been reported to correlate with tumor progression and poor prognosis in colorectal cancer. However, the relevance of CD44s and CD44v6 to epithelial-mesenchymal transition (EMT) remains unclear. Immunohistochemistry was performed to investigate the clinical importance of CD44s and CD44v6 and their relevance to EMT in 113 patients with stage II/III colorectal cancer treated by curative resection. The relevance of CD44v6 knockdown to the phenotype of colon cancer cells was examined using small interfering RNA (siRNA) specific for CD44v6 in vitro. CD44v6 expression showed a significant inverse correlation with E-cadherin expression (P=0.0007) and a positive correlation with vimentin expression (P=0.0096). A multivariate analysis showed that high CD44v6 expression was an independent poor prognostic factor for disease-free survival (P=0.01, HR=3.05) and overall survival (P=0.025, HR=3.16). The clinical significance and the relevance of CD44s expression to EMT markers was noted to a lesser extent compared to CD44v6 expression. The knockdown of CD44v6 decreased vimentin expression, cell invasion and HGF-induced cell migration, but conferred only a slight effect on E-cadherin expression in colon cancer cells (HCT116 and LoVo). CD44v6 is related to poor outcome of patients with colorectal cancer via upregulation of the mesenchymal phenotype.

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