Meng Xiaodan, Schwarzenbach Heidi, Yang Yifeng, Müller Volkmar, Li Nan, Tian Dongmei, Shen Yan, Gong Zhaohui
Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China.
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
Transl Oncol. 2019 Sep;12(9):1213-1220. doi: 10.1016/j.tranon.2019.05.015. Epub 2019 Jul 2.
As peripheral blood contains fluctuated levels of circulating cell-free mitochondrial DNA (ccf mtDNA), we aimed to evaluate ccf mtDNA as a biomarker for diagnosis and prognosis of epithelial ovarian cancer (EOC). In the present study, we recruited 165 EOC patients and 60 healthy women. Quantitative RT-PCR was applied to amplify 79-bp and 230-bp fragments of the mitochondrial 16 s RNA gene in sera of these participants. MtDNA integrity was defined as the ratio of long to short mtDNA fragments. We observed that the levels of mtDNA79 and mtDNA230 were significantly increased (P = .0001), whereas the mtDNA integrity (P = .0001) was decreased in EOC patients compared with those in healthy controls. MtDNA79 showed a sensitivity of 90.3% and a specificity of 81.7% (AUC = 0.900) to discriminate EOC from healthy controls. Moreover, the amounts of mtDNA79 (P = .0001, P = .012, P = .039) and mtDNA230 (P = .0001, P = .042) continuously raised from healthy controls over FIGO I-II to FIGO III and IV, with highest levels of mtDNA79 (P = .0001) and mtDNA230 (P = .0001) in FIGO III and IV. Increasing levels of mtDNA79 (P = .003, P = .0001) and mtDNA230 (P = .041, P = .0001) were also associated with lymph node metastasis and CA125 values. The higher levels of mtDNA79 (P = .0001; HR 3.2, 95%CI:1.6-6.3) and mtDNA230 (borderline P = .048, HR 0.9, 95%CI:0.9-1.0) also correlated with poor patients' overall survival, of which mtDNA79 could act as an independent factor for overall survival. Our data show a significant association of increasing levels of ccf mtDNA with EOC progress and poor prognosis.
由于外周血中循环游离线粒体DNA（ccf mtDNA）水平存在波动，我们旨在评估ccf mtDNA作为上皮性卵巢癌（EOC）诊断和预后生物标志物的价值。在本研究中，我们招募了165例EOC患者和60名健康女性。应用定量逆转录聚合酶链反应（qRT-PCR）扩增这些参与者血清中线粒体16 s RNA基因的79-bp和230-bp片段。线粒体DNA完整性定义为长片段与短片段线粒体DNA的比率。我们观察到，与健康对照相比，EOC患者的mtDNA79和mtDNA230水平显著升高（P = 0.0001），而线粒体DNA完整性（P = 0.0001）降低。mtDNA79区分EOC与健康对照的敏感性为90.3%，特异性为81.7%（曲线下面积[AUC]=0.900）。此外，从健康对照到国际妇产科联盟（FIGO）I-II期，再到FIGO III期和IV期，mtDNA79（P = 0.0001、P = 0.012、P = 0.039）和mtDNA230（P = 0.0001、P = 0.042）的量持续升高，并在FIGO III期和IV期达到最高水平（mtDNA79，P = 0.0001；mtDNA230，P = 0.0001）。mtDNA79（P = 0.003、P = 0.0001）和mtDNA230（P = 0.041、P = 0.0001）水平升高也与淋巴结转移和CA125值相关。mtDNA79（P = 0.0001；风险比[HR] 3.2，95%置信区间[CI]：1.6-6.3）和mtDNA230（临界P = 0.048，HR 0.9，95%CI：0.9-1.0）水平较高也与患者总生存期较差相关，其中mtDNA79可作为总生存期的独立因素。我们的数据表明，ccf mtDNA水平升高与EOC进展和不良预后显著相关。
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