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  • br Regarding the mtDNA integrity which is determined


    Regarding the mtDNA integrity, which is determined by the ratio of mtDNA230 to mtDNA79, compared with the healthy controls, EOC patients showed lower levels of the mtDNA integrity. Our findings show that there was more abundant mtDNA79 than
    1220 Circulating mtDNA as diagnostic and prognostic biomarker in EOC Meng et al. Translational Oncology Vol. 12, No. 9, 2019
    mtDNA230 circulating in the serum of EOC patients, implying an active apoptotic phenomenon in EOC. However, the mtDNA integrity could not differentiate between less and more aggressive EOC, and had no relationships with CA125 values and patients' overall survival, indicating that the mtDNA integrity rather reflects the state and source of mtDNA than pathological conditions. So far, the pathophysiological mechanisms leading to the increase in ccf mtDNA in EOC remain largely enigmatic, but it is hypothesized that the excessive release by apoptotic or necrotic KRN 7000 and the reduced clearance by inflammatory cells during tumor development may contribute to the altered mtDNA content. Additionally, ccf mtDNA not only circulates in a cell-free form, but also in a particle-associated form [21], which protects mtDNA from digestion by DNase.
    Although there are increasing publications reporting the possible usefulness of circulating mtDNA content as diagnostic or prognostic factor in other tumor types, such as non-Hodgkin lymphoma [22], lung cancer [16], pancreatic cancer [23], breast cancer [24], prostate cancer [25], hepatocellular carcinoma [26], renal cell carcinoma [27] or glioma [28], prior to the application of ccf mtDNA as a noninvasive biomarker in clinic, large-scaled multicenter studies with long follow-up data are necessary to confirm the clinical relevance of ccf mtDNA.
    In summary, in our study, we show that the abnormal high levels of serum mtDNA79 and mtDNA230 are accompanied by advanced EOC, and related to poor patients' overall survival. These results provide an alternative to utilize ccf mtDNA as a noninvasive tool for the diagnosis and prognosis of EOC.
    This study was supported by the research grants from the Natural Science Foundation of Zhejiang (LQ18H200001), the Non-profit Technology Research Program of Zhejiang (LGF18H160006), the Non-profit Technology Research Program of Ningbo (2019C50040), the Natural Science Foundation of Ningbo (2018A610204), the Scientific Innovation Team Project of Ningbo (2017C110019) and the K.C. Wong Magna Fund in Ningbo University.
    [2] Tuboly E, McLlroy D, Briggs G, Lott N, and Balogh ZJ (2017). Clinical implications and pathological associations of circulating mitochondrial DNA. Front Biosci (Landmark Ed) 22, 1011–1022.
    [4] Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN, and Vandenabeele P (2011). Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol 32, 157–164.
    [6] Arshad O, Gadawska I, Sattha B, Cote HCF, and Hsieh AYY (2018). Elevated cell-free mitochondrial DNA in filtered plasma Is Associated With HIV Infection and Inflammation. J Acquir Immune Defic Syndr 78, 111–118.
    [7] Borghini A, Mercuri A, Turchi S, Chiesa MR, Piccaluga E, and Andreassi MG (2015). Increased circulating cell-free DNA levels and mtDNA fragments in interventional cardiologists occupationally exposed to low levels of ionizing radiation. Environ Mol Mutagen 56, 293–300. 
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