Analysis of specialized DNA polymerases expression in human gliomas: association with prognostic significance.
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 κ (Pol κ), Pol ι, and Pol η 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 κ and Pol ι was observed in 57.5% (23-40) and 27.5% (11-40) of patients, respectively, whereas no significant expression of Pol η was seen in the specimens. Immunohistochemical studies revealed positive Pol κ and Pol ι staining in 72 (69.2%) and 33 (31.7%) of the 104 glioma specimens, respectively. Pol κ expression was associated with advanced stages of the disease. Both Pol κ- and Pol ι-positive staining were associated with shorter survival in glioma patients (P < .001 and P = .014, respectively). A multivariate survival analysis identified Pol κ as an independent prognostic factor for glioma patients (P < .001). These findings demonstrate, for the first time, that the expression of Pol κ and Pol ι is deregulated in gliomas, and upregulation of Pol κ is associated with poorer prognosis in glioma patients.
Wang
Huibo
H
State Key Laboratory of Genetic Engineering, Center for Fudan-VARI Genetics Epidemiology and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
Wu
Wenting
W
Wang
Hong-Wei
HW
Wang
Shuai
S
Chen
Yuanyuan
Y
Zhang
Xiaotian
X
Yang
Jingmin
J
Zhao
Shiguang
S
Ding
Han-Fei
HF
Lu
Daru
D
D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D019951:DNA Polymerase beta / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000099270:Y-Family DNA Polymerases
D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; C415367:DNA polymerase beta2; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases