Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer

Xu, Hui; He, Wei; Jiang, Hui; Zhao, Hong; Peng, Xiaohong; Wei, Yuehua; Wei, Jing-Ni; Xie, Conghua; Liang, Changhong; Ye, Zhong; Zhang, Gong; Deng, Di; Zhou, Youwen; Zhou, Fen

doi:10.3892/or.2013.2783

Cited by 26 publications

(15 citation statements)

References 29 publications

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“…After a thorough review of titles and abstracts by two investigators independently, 394 studies were excluded and the full texts of remaining 26 references have also been artificial retrieved for further identification. Finally a total of 20 retrospective studies comprising 5413 patients were included in our study and 18 studies were used for analysis16171819202122252627282930313233343536. Among the included studies for analysis, there were 16 studies recruited Asian patients while 2 studies recruited Caucasian patients.…”

Section: Resultsmentioning

confidence: 99%

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Chen

Wen

Sun

et al. 2016

Sci Rep

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Previous studies have suggested that mitochondrial DNA (mtDNA) copy number was associated with cancer risk. However, no solid conclusion revealed the potential predictive value of mtDNA copy number for cancer prognosis. The present meta-analysis was performed to clarify the problem. Hence, we performed a systematic search in PubMed, EmBase, Web of Science databases independently and a total of eighteen studies comprising 3961 cases satisfied the criteria and finally enrolled. Our results didn’t show the association between them but significant heterogeneity in overall analysis (OS: HR = 0.923, 95% CI: 0.653–1.306, p = 0.652; DFS: HR = 0.997, 95% CI: 0.599–1.659, p = 0.99). However, subgroup analysis stratified by sample came to the opposite conclusion. High level mitochondrial DNA copy number in peripheral blood predicted a poor cancer prognosis (OS: HR = 1.624, 95% CI: 1.211–2.177, p = 0.001; DFS: HR = 1.582, 95% CI: 1.026–2.439, p = 0.038) while patients with high level mitochondrial DNA copy number in tumor tissue exhibited better outcomes (OS: HR = 0.604 95% CI: 0.406–0.899, p = 0.013; DFS: HR = 0.593, 95% CI: 0.411–0.857, p = 0.005). These findings were further proved in detailed analyses in blood or tissue subgroup. In conclusion, our study suggested the elevated mtDNA copy number in peripheral blood predicted a poor cancer prognosis while the better outcome was presented among patients with elevated mtDNA copy number in tumor tissue.

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Section: Resultsmentioning

confidence: 99%

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Chen

Wen

Sun

et al. 2016

Sci Rep

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“…In brief, the PCR products were digested by 2 U DdeI (New England Biolabs, Ipswich, MA, USA) at 37°C for 4 h, in which the mtDNA A10398G allele A yielded two fragments including 128 bp and 73 bp, allele G yielded three fragments including 90 bp, 73 bp, and 38 bp. The digestion products were analyzed directly by a 2% agarose gel, as published in our previous paper . To confirm the accuracy of the method used, the genotypes were confirmed by DNA sequencing analysis, and, at the same time, approximately 10% of the samples were randomly selected to repeat the assays.…”

Section: Methodsmentioning

confidence: 99%

Peripheral blood mitochondrial DNA content, A10398G polymorphism, and risk of breast cancer in a Han Chinese population

Jiang

Zhao

Xu³

et al. 2014

Cancer Science

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It has been reported that quantitative alterations and sequence variations of mtDNA are associated with the onset and progression of particular types of tumor. However, the relationship between mtDNA content, certain mtDNA polymorphisms in peripheral blood leukocytes and breast cancer risk remain obscure. This study was undertaken to investigate whether mtDNA content and the A10398G polymorphism in peripheral blood leukocytes could be used as risk predictors for breast cancer in Han Chinese women. Blood samples were obtained from a total of 506 breast cancer patients and 520 matched healthy controls. The mtDNA content was measured by using quantitative real-time PCR assay; A10398G polymorphism was determined by PCR-RFLP assay. There was no statistically significant difference between cases and controls in terms of peripheral blood mtDNA content or A10398G polymorphism. However, further analysis suggested that the risk of breast cancer was associated with decreased mtDNA content in premenopausal women (P = 0.001; odds ratio = 0.54; 95% confidence interval, 0.38–0.77), with increased mtDNA content in postmenopausal women (P = 0.027; odds ratio = 1.49; 95% confidence interval, 1.05–2.11). In addition, the associations between mtDNA content and several clinicopathological parameters of cases such as age, menopausal status, and number of pregnancies and live births were observed. This case–control study indicated that the peripheral blood mtDNA content might be a potential biomarker to evaluate the risk of breast cancer for selected Chinese women.

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“…For example, a previous study demonstrated that African-American female patients with the wild-type mtDNA 10398A allele had a significantly increased risk of invasive breast cancer (20). In addition, the wild-type mtDNA 10398A variant in African American women with breast cancer provides resistance to cell apoptosis and promotes metastasis in mice (22). In NSCLC, patients with a high mtDNA content in combination with the mutant mtDNA 10398G allele had a significantly increased overall survival time compared with those that had a low mtDNA content and the wild-type mtDNA 10398A allele (19).…”

Section: Discussionmentioning

confidence: 99%

Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer

Wei

Wang

et al. 2016

Oncology Letters

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Mitochondrial dysfunction is associated with pathogenic mitochondrial (mt)DNA mutations. The majority of mtDNA point mutations have a heteroplasmic status, which is defined as the coexistence of wild-type and mutated DNA within a cell or tissue. Previous findings demonstrated that certain mtDNA heteroplasmic mutations contribute to widely spread chronic diseases, including cancer, and alterations in the heteroplasmy level are associated with the clinical phenotype and severity of cancer. In the present study, the proportions of mutant mtDNA 10398G were assessed using amplification-refractory mutation system-quantitative polymerase chain reaction (PCR) assay in 129 non-small cell lung cancer (NSCLC) tissue samples. Wild-type and mutant sequences were separately amplified using allele-specific primers and, subsequently, the PCR products containing the mtDNA 10398 site were ligated into vectors to construct a standard plasmid DNA construct. The association between mtDNA A10398G and the prognosis of patients was analyzed by survival analysis and Cox proportional hazards model. For the patient cohort, the median follow-up time and overall survival time were 20.6 and 26.3 months, respectively. The ratios of mutant heteroplasmy ranged between 0.31 and 97.04%. Patients with a high degree of mutant mtDNA 10398G had a significantly longer overall survival time compared with those with a low degree of mutant mtDNA 10398G (28.7 vs. 22.5 months, respectively; P<0.05). In addition, multivariate analysis demonstrated that epidermal growth factor receptor mutation status, tumor stage and the possession of a low degree of mutant 10398G were the three most independent prognostic factors. In conclusion, the present study suggests that, among NSCLC patients, there are large shifts in mutant mtDNA 10398G heteroplasmy and a low degree of mutant mtDNA 10398G heteroplasmy may be a marker of poor prognosis in patients with NSCLC.

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Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer

Cited by 26 publications

References 29 publications

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis

Peripheral blood mitochondrial DNA content, A10398G polymorphism, and risk of breast cancer in a Han Chinese population

Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer

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