Abstract | BACKGROUND: The double-strand break ( DSB) repair capacity has been implicated in the survival of patients in several cancer types. However, little is known about the prognostic importance of the key DSB repair genes- ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase catalytic subunit ( DNA- PKcs), and the Ku heterodimeric regulatory complex 86-kD subunit (Ku80)-in nonsmall cell lung cancer (NSCLC). To address this issue, the authors determined the messenger RNA ( mRNA) expression of these genes in patients NSCLC and assessed their prognostic relevance. METHODS:
mRNA expression levels of ATM, DNA- PKcs, and Ku80 were measured in tumor and adjacent normal tissues from 140 patients with NSCLC by using quantitative real-time polymerase chain reaction analysis. Then, a Cox proportional hazards regression model and Kaplan-Meier plots were used to evaluate the association between the tumor:normal (T/N) expression ratios of the 3 genes and the overall survival rate and duration in patients with NSCLC. RESULTS:
mRNA expression of ATM and DNA- PKcs, but not of Ku80, was significantly higher in tumor tissues than in adjacent normal tissues (P=.003 and P<.001, respectively). The high T/N expression ratios of ATM and DNA- PKcs were associated significantly with a 1.82-fold increased risk of death (95% confidence interval, 1.05-2.70) and a 2.13-fold increased risk of death (95% confidence interval, 1.21-3.76), respectively. However, no significant association with risk was observed for Ku80. Kaplan-Meier analyses revealed that patients with high T/N expression ratios of ATM or DNA- PKcs had notably shorter median survival than patients with low ratios. CONCLUSIONS: The current findings suggested that the T/N expression ratios of ATM and DNA- PKcs may be useful for identifying NSCLC patients with a poor prognosis who may benefit from more aggressive therapy.
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Authors | Jinliang Xing, Xifeng Wu, Ara A Vaporciyan, Margaret R Spitz, Jian Gu |
Journal | Cancer
(Cancer)
Vol. 112
Issue 12
Pg. 2756-64
(Jun 15 2008)
ISSN: 0008-543X [Print] United States |
PMID | 18457328
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright (c) 2008 American Cancer Society. |
Chemical References |
- Antigens, Nuclear
- Cell Cycle Proteins
- DNA-Binding Proteins
- RNA, Messenger
- Tumor Suppressor Proteins
- ATM protein, human
- Ataxia Telangiectasia Mutated Proteins
- DNA-Activated Protein Kinase
- Protein Serine-Threonine Kinases
- Xrcc6 protein, human
- Ku Autoantigen
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Topics |
- Aged
- Antigens, Nuclear
(chemistry, metabolism)
- Ataxia Telangiectasia Mutated Proteins
- Carcinoma, Non-Small-Cell Lung
(metabolism)
- Catalytic Domain
(genetics)
- Cell Cycle Proteins
(metabolism)
- DNA-Activated Protein Kinase
(genetics, metabolism)
- DNA-Binding Proteins
(chemistry, metabolism)
- Female
- Humans
- Ku Autoantigen
- Lung Neoplasms
(metabolism)
- Male
- Middle Aged
- Mutation
- Prognosis
- Protein Serine-Threonine Kinases
(metabolism)
- RNA, Messenger
(metabolism)
- Survival Rate
- Tumor Suppressor Proteins
(metabolism)
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