title: CD133 in brain tumor: the prognostic factor.
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.
authors.affiliation: Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR, Singapore.
authors.forename: Hiu Fung
authors.initials: HF
authors.lastname: Yuen
authors.affiliation: Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
authors.forename: Xinping
authors.initials: X
authors.lastname: Xi
authors.affiliation: Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
authors.forename: Peng
authors.initials: P
authors.lastname: Lyu
authors.affiliation: Department of Pathology, University of Hong Kong, Hong Kong.
authors.forename: Kwok Wah
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, Londonderry, United Kingdom.
authors.forename: Shu Dong
authors.initials: SD
authors.lastname: Zhang
authors.affiliation: Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
authors.forename: Hang Fai
authors.initials: HF
authors.lastname: Kwok
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005801:Genes, Homeobox / Q000235:genetics; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000071916:AC133 Antigen; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D005136:Eye Proteins; C044539:LIM2 protein, human; D008565:Membrane Proteins; C000606023:PROM1 protein, human; D014750:Vincristine; D014747:Vinblastine
keywords: CD133; HOX; LIM2; brain tumor; stem cell