Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival

Tal Shahar, Uri Rozovski, Kenneth R. Hess, Anwar Hossain, Joy Gumin, Feng Gao, Gregory N. Fuller, Lindsey Goodman, Erik P. Sulman, Frederick F. Lang

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method. We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database. Results. In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P =.02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P =.04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P =.04), respectively. Conclusions. The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas.

Original languageEnglish
Pages (from-to)660-668
Number of pages9
JournalNeuro-Oncology
Volume19
Issue number5
DOIs
StatePublished - 1 May 2017
Externally publishedYes

Keywords

  • Glioblastoma
  • Mesenchymal stem cells
  • Microenvironment
  • Prognosis

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