Oncotarget

Research Papers:

CD133 in brain tumor: the prognostic factor

Bin Li, Cian M. McCrudden, Hiu Fung Yuen, Xinping Xi, Peng Lyu, Kwok Wah Chan, Shu Dong Zhang and Hang Fai Kwok _

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Oncotarget. 2017; 8:11144-11159. https://doi.org/10.18632/oncotarget.14406

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Abstract

Bin Li1, Cian M. McCrudden2, Hiu Fung Yuen3, Xinping Xi1, Peng Lyu1, Kwok Wah Chan4, Shu Dong Zhang5, Hang Fai Kwok1

1Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR

2School of Pharmacy, Queen’s University Belfast, Belfast, United Kingdom

3Institute of Molecular and Cell Biology, A*STAR, Singapore

4Department of Pathology, University of Hong Kong, Hong Kong

5Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, Londonderry, United Kingdom

Correspondence to:

Hang Fai Kwok, email: [email protected]

Keywords: brain tumor, CD133, HOX, LIM2, stem cell

Received: April 13, 2016     Accepted: December 26, 2016     Published: December 31, 2016

ABSTRACT

CD133 has been shown to be an important stem cell factor that promotes glioma progression. However, the mechanism for CD133-mediated glioma progression has yet to be fully elucidated. In this study, we found that CD133 mRNA expression was a prognostic marker in three independent glioma patient cohorts, corroborating a putative role for CD133 in glioma progression. Importantly, we found that CD133 expression in glioma was highly correlated with the expression of HOX gene stem cell factors (HOXA5, HOXA7, HOXA10, HOXC4 and HOXC6). The expression of these HOX genes individually was significantly associated with survival. Interestingly, the prognostic significance of CD133 was dependent on the expression level of HOX genes, and vice versa. CD133 (p = 0.021) and HOXA7 (p = 0.001) were independent prognostic markers when the three glioma patient cohorts were combined (n = 231). Our results suggest that HOX genes may play a more important role in progression of glioma when CD133 expression is low. Furthermore, we showed that low-level expression of LIM2 in CD133-high glioma was associated with poorer survival, suggesting that LIM2 could be a therapeutic target for glioma expressing a high level of CD133. Connectivity mapping identified vinblastine and vincristine as agents that could reverse the CD133/HOX genes/LIM2-signature, and we confirmed this by in vitro analysis in glioma cell lines, demonstrating that CD133 and HOX genes were co-expressed and could be downregulated by vincristine. In conclusion, our data show that CD133 and HOX genes are important prognostic markers in glioma and shed light on possible treatment strategies for glioma expressing a high level of CD133.


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