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Article

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

  • Authors:
    • Hui Xu
    • Wei He
    • Huan-Gang Jiang
    • Hong Zhao
    • Xiao-Hong Peng
    • Yue-Hua Wei
    • Jing-Ni Wei
    • Cong-Hua Xie
    • Chen Liang
    • Ya-Hua Zhong
    • Gong Zhang
    • Di Deng
    • Yun-Feng Zhou
    • Fu-Xiang Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuchang, Wuhan, Hubei 430071, P.R. China
  • Pages: 3006-3012
    |
    Published online on: October 3, 2013
       https://doi.org/10.3892/or.2013.2783
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Abstract

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality worldwide. Mitochondrial dysfunction has been postulated to render cancer cells resistant to apoptosis based on the Warburg hypothesis. However, few studies have investigated the prognostic value of mitochondrial DNA (mtDNA) content and G10398A polymorphism in NSCLC patients. mtDNA copy number and G10398A polymorphism in 128 NSCLC tissue samples were assessed by real-time PCR (RT-PCR) and PCR-RFLP respectively, and their relationship to prognosis were analyzed by survival analysis and Cox proportional hazards model. In vitro, an mtDNA deletion A549 ρ0 cell model was utilized to assess the function of mtDNA on radiosensitivity. Cell cycle distribution and reactive oxygen species (ROS) were analyzed to elucidate the potential mechanisms. For the whole group, the median follow-up time and overall survival time were 22.5 and 23.4 months, respectively. Patients with high mtDNA content had a marginally longer survival time than patients with low mtDNA content (P=0.053). Moreover, patients with high mtDNA content plus 10398G had a significantly longer overall survival time compared with those having low mtDNA content plus 10398A (47 vs. 27 months, P<0.05). In addition, multivariate analysis showed that stage and low mtDNA content plus 10398A were the two most independent prognostic factors. In vitro, the A549 ρ0 cells showed more resistance to radiation than ρ+ cells. Following radiation, ρ0 cells showed delayed G2 arrest and lower ROS level as compared to ρ+ cells. In conclusion, the present study suggests that in patients with NSCLC, low mtDNA content plus 10398A could be a marker of poor prognosis which is associated with resistance to anticancer treatment caused by low mtDNA content plus 10398A polymorphism resulting in mitochondrial dysfunction.
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Copy and paste a formatted citation
Spandidos Publications style
Xu H, He W, Jiang H, Zhao H, Peng X, Wei Y, Wei J, Xie C, Liang C, Zhong , Zhong , et al: Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer. Oncol Rep 30: 3006-3012, 2013.
APA
Xu, H., He, W., Jiang, H., Zhao, H., Peng, X., Wei, Y. ... Zhou, F. (2013). Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer. Oncology Reports, 30, 3006-3012. https://doi.org/10.3892/or.2013.2783
MLA
Xu, H., He, W., Jiang, H., Zhao, H., Peng, X., Wei, Y., Wei, J., Xie, C., Liang, C., Zhong, ., Zhang, G., Deng, D., Zhou, Y., Zhou, F."Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer". Oncology Reports 30.6 (2013): 3006-3012.
Chicago
Xu, H., He, W., Jiang, H., Zhao, H., Peng, X., Wei, Y., Wei, J., Xie, C., Liang, C., Zhong, ., Zhang, G., Deng, D., Zhou, Y., Zhou, F."Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer". Oncology Reports 30, no. 6 (2013): 3006-3012. https://doi.org/10.3892/or.2013.2783
Copy and paste a formatted citation
x
Spandidos Publications style
Xu H, He W, Jiang H, Zhao H, Peng X, Wei Y, Wei J, Xie C, Liang C, Zhong , Zhong , et al: Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer. Oncol Rep 30: 3006-3012, 2013.
APA
Xu, H., He, W., Jiang, H., Zhao, H., Peng, X., Wei, Y. ... Zhou, F. (2013). Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer. Oncology Reports, 30, 3006-3012. https://doi.org/10.3892/or.2013.2783
MLA
Xu, H., He, W., Jiang, H., Zhao, H., Peng, X., Wei, Y., Wei, J., Xie, C., Liang, C., Zhong, ., Zhang, G., Deng, D., Zhou, Y., Zhou, F."Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer". Oncology Reports 30.6 (2013): 3006-3012.
Chicago
Xu, H., He, W., Jiang, H., Zhao, H., Peng, X., Wei, Y., Wei, J., Xie, C., Liang, C., Zhong, ., Zhang, G., Deng, D., Zhou, Y., Zhou, F."Prognostic value of mitochondrial DNA content and G10398A polymorphism in non-small cell lung cancer". Oncology Reports 30, no. 6 (2013): 3006-3012. https://doi.org/10.3892/or.2013.2783
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