4.6 Article

miR-182 as a Prognostic Marker for Glioma Progression and Patient Survival

Journal

AMERICAN JOURNAL OF PATHOLOGY
Volume 177, Issue 1, Pages 29-38

Publisher

ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.090812

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Funding

  1. Ministry of Science and Technology of China(973) [2005CB724605]
  2. Natural Science Foundation of China [30670803, 30770836, 30771110, 30870963, 30831160517]
  3. Program for New Century Excellent Talents in Universities [NCET-07-0877]
  4. Science and Technology Department of Guangdong Province, China [07001503, 8251008901000006, 2008A030201006]
  5. Ministry of Education of China [(2008)890, 200805580047]
  6. Science and Technology Department of Zhuhai Municipality
  7. Guangdong Provincial Natural Science Foundation
  8. US NIH [CA102011, CA130966]
  9. ACS RSG [CSM-107111]

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Accumulating evidence indicates that miRNA expression can be used as a diagnostic and prognostic marker for human cancers. We report that the expression level of miR-182 was markedly up-regulated in glioma cell lines and in human primary glioma specimens. Quantitative PCR analysis showed that miR182 was significantly increased by up to 32-fold in glioma tumors compared with the adjacent nontumor brain tissues obtained from the same patient. Elevated expression of miR-182 was further identified by in situ hybridization in 248 of 253 (98%) archived human glioma biopsies tested. Statistical analysis revealed a significant correlation between miR-182 expression and World Health Organization glioma grading (P < 0.001). The cumulative 5-year survival rate of glioma patients was 51.54% (95% confidence interval, 0.435 to 0.596) in the low miR-182-expression group, whereas it was only 7.23% (95% confidence interval, 0.027 to 0.118) in the high miR-182-expression group (P = 0.001), and multivariate Cox regression analysis indicated that miR-182 expression was an independent prognostic indicator for the survival of glioma patients. Moreover, the correlations of miR-182 level with the clinical features of glioma suggested in the in situ hybridization analysis were further verified by the real-time RT-PCR analysis. Taken together, our results suggest that miR-182 could be a valuable marker of glioma progression and that high miR-182 expression is associated with poor overall survival in patients with malignant glioma. (Am J Pathol 2010, 177:29-38 DOI: 10.2353/ajpath.2010.090812)

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