Overexpression of CD44 is associated with a poor prognosis in grade II/III gliomas

  • Chongxian Hou
  • Yukitomo Ishi
  • Hiroaki Motegi
  • Michinari Okamoto
  • Yafei Ou
  • Jiawei Chen
  • Shigeru YamaguchiEmail author
Laboratory Investigation



Overexpression of CD44 has been detected in many types of tumor tissues. Moreover, CD44 is recognized as a cancer stem cell marker for many cancers. However, the prognostic value of CD44 for glioma patients has not yet been clarified. The authors tried to explore the impact of CD44 expression on grade II/III glioma patients.


To assess the RNA expression levels of CD44 in glioma tissues and normal brain tissues, meta-analyses were conducted in the online Oncomine database. The mRNA expression levels of CD44, CD44s, and CD44v2–v10 in 112 grade II/III glioma patients in Hokkaido University Hospital (HUH) were detected by qPCR. The RNA-seq data and clinical data of grade II/III glioma patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases.


Based on the Oncomine database, CD44 has significantly high expression in glioma tissues as compared with normal tissues. We explored the clinical relevance of CD44 mRNA expression based on the HUH cohorts, the TCGA cohorts, and the CGGA cohorts. In survival analysis, high mRNA expression of CD44 was correlated with poor overall survival and poor progression-free survival in grade II/III glioma patients. Multivariate Cox regression analyses confirmed CD44 as an independent prognostic factor for grade II/III glioma patients.


The present study suggests that overexpression of CD44 is associated with a poor prognosis for grade II/III glioma patients. Moreover, our findings suggest that CD44 could serve as a prognostic biomarker in grade II/III glioma patients.


CD44 Glioma Prognostic factor Biomarker 



We would like to thank Mr. Xie Tao for the English language review.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The present study was approved by the local Ethics Committee at Hokkaido University Hospital (Sapporo, Japan; 015–0154). As this study was retrospective, informed consent was waived by the IRB. All procedures performed in the present study were in accordance with 1964 Helsinki Declaration and its later amendments.

Supplementary material

11060_2019_3288_MOESM1_ESM.tif (1.9 mb)
Oncomine microarray database was used to evaluate the mRNA expression of CD44 in glioma tissues vs. normal brain tissues. a Nine microarray datasets containing 18 groups regarding mRNA expression of CD44 in glioma tissues vs. normal brain tissues were involved in this meta-analysis. b A meta-analysis of five microarray datasets containing ten groups regarding mRNA expression of CD44 in grade II/III glioma tissues vs. normal brain tissues. c A meta-analysis of six microarray datasets containing six groups regarding mRNA expression of CD44 in GBM tissues vs. normal brain tissues. d Box plots derived from gene expression data of each group comparing expression of CD44 in glioma tissues and normal brain tissues are shown. Data are shown as a median rank of CD44 through each dataset analysis. The P value for CD44 was presented using the median ranked analysis about glioma vs. normal tissues—Supplementary Fig. 1 (TIFF 1934 kb)
11060_2019_3288_MOESM2_ESM.tif (931 kb)
The correlation between CD44 mRNA expression and OS of glioma patients. a–c The association between CD44 mRNA expression and OS in grade II gliomas. d–f The association between CD44 mRNA expression and OS in grade III gliomas. g–i The association between CD44 mRNA expression and OS in IDH mutant gliomas. j–l The association between CD44 mRNA expression and OS in IDH wild type gliomas—Supplementary Fig. 2 (TIFF 931 kb)
11060_2019_3288_MOESM3_ESM.docx (25 kb)
Supplementary Tables (DOCX 25 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, Faculty of MedicineHokkaido UniversitySapporoJapan
  2. 2.Graduate School of Information Science and TechnologyHokkaido UniversitySapporoJapan
  3. 3.Shantou University Medical CollegeShantouChina

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