Analysis of specialized DNA polymerases expression in human gliomas: Association with prognostic significance

Huibo Wang, Wenting Wu, Hong Wei Wang, Shuai Wang, Yuanyuan Chen, Xiaotian Zhang, Jingmin Yang, Shiguang Zhao, Han Fei Ding, Daru Lu

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Aberrant activation of the translesion DNA synthesis (TLS) pathway has been suggested to play a role in tumorigenesis by promoting genetic mutations. We therefore examined glioma specimens for the expression of specialized DNA polymerases involved in TLS and assessed their prognostic significance. The expression levels of DNA polymerase k (Pol k), Pol i, and Pol h were assessed in 40 primary glioma samples and 10 normal brain samples using quantitative real-time PCR and Western blot analysis. Their prognostic significance was evaluated using a population-based tissue microarray derived from a cohort of 104 glioma patients. Overexpression of Pol k and Pol i was observed in 57.5%(23-40) and 27.5% (11-40) of patients, respectively, whereas no significant expression of Pol h was seen in the specimens. Immunohistochemical studies revealed positive Pol k and Pol i staining in 72 (69.2%) and 33 (31.7%) of the 104 glioma specimens, respectively. Pol k expression was associated with advanced stages of the disease. Both Pol k- and Pol i- positive staining were associated with shorter survival in glioma patients (P < .001 and P 5 .014, respectively). A multivariate survival analysis identified Pol k as an independent prognostic factor for glioma patients (P < .001). These findings demonstrate, for the first time, that the expression of Pol k and Pol i is deregulated in gliomas, and upregulation of Pol k is associated with poorer prognosis in glioma patients.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalNeuro-Oncology
Volume12
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • Glioma
  • Mutagenesis
  • Prognosis
  • Specialized polymerase
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Wang, H., Wu, W., Wang, H. W., Wang, S., Chen, Y., Zhang, X., Yang, J., Zhao, S., Ding, H. F., & Lu, D. (2010). Analysis of specialized DNA polymerases expression in human gliomas: Association with prognostic significance. Neuro-Oncology, 12(7), 679-686. https://doi.org/10.1093/neuonc/nop074