Circulating cell‐free nuclear DNA (nDNA) has been implicated in individual cancer types with a diagnostic value; however, the role of cell‐free mitochondrial DNA (mtDNA) in cancers is controversial. We aimed to investigate and compare the diagnostic potential of both nDNA and mtDNA for multiple cancers and to investigate their ability to distinguish multiple cancers from healthy controls and from nonmalignant diseases. We also investigated the prognostic value of both nDNA and mtDNA. The absolute copy number of circulating DNAs in suspected cancer patients (n = 286) referred to a cancer diagnostic center and healthy controls (n = 109) was quantified by droplet digital polymerase chain reaction. Among the suspected cancer patients, 66 (23%) were diagnosed with various cancers, 193 (67%) with nonmalignant diseases, and 27 (10%) with no active disease. Levels of nDNA were significantly higher in cancers (copies/μl; mean ± SD, 21.0 ± 14.2) as compared with nonmalignant diseases (15.2 ± 10.0) and controls (9.3 ± 4.1). In contrast, levels of mtDNA were significantly lower in cancers (copies/μl; mean ± SD, 68,557 ± 66,663) and nonmalignant diseases (60,174 ± 55,831) as compared with controls (98,714 ± 77,789). Receiver operating curve analysis showed that nDNA not only could distinguish multiple cancers from controls (area under curve [AUC] = 0.78; 95% confidence interval [CI] = 0.70–0.86) but also from nonmalignant diseases (AUC = 0.68; 95% CI = 0.59–0.76). However, mtDNA could only differentiate cancers from controls (AUC = 0.65; 95% CI = 0.56–0.73). Higher levels of nDNA were also associated with increased mortality in the cancer patients (hazard ratio = 2.3; 95% CI = 1.1–4.7). Circulating cell‐free nDNA, but not the mtDNA, could distinguish multiple cancers from nonmalignant diseases and was associated with poor survival of cancer patients.

中文翻译：

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循环性无细胞核和线粒体DNA对多种癌症和非恶性疾病的诊断潜力：对可疑癌症患者的研究

循环中的无细胞核DNA（nDNA）与个别癌症类型有关，具有诊断价值。然而，无细胞线粒体DNA（mtDNA）在癌症中的作用是有争议的。我们旨在调查和比较nDNA和mtDNA在多种癌症中的诊断潜力，并研究它们区分健康对照和非恶性疾病中多种癌症的能力。我们还研究了nDNA和mtDNA的预后价值。疑似癌症患者中循环DNA的绝对拷贝数（n  = 286）指癌症诊断中心和健康对照（n ＝ 109）通过液滴数字聚合酶链反应定量。在可疑的癌症患者中，有66名（23％）被诊断出患有各种癌症，有193名（67％）被诊断为非恶性疾病，而27名（10％）没有活动性疾病。与非恶性疾病（15.2±10.0）和对照（9.3±4.1）相比，癌症中的nDNA水平显着更高（拷贝/微升；平均值±  SD，21.0±14.2）。相比之下，癌症中mtDNA的水平明显更低（份数/μl；平均值±  SD（68,557±66,663）和非恶性疾病（60,174±55,831），而对照组（98,714±77,789）。受体工作曲线分析显示，nDNA不仅可以区分多种癌症与对照（曲线下面积[AUC] = 0.78； 95％置信区间[CI] = 0.70–0.86），而且还可以与非恶性疾病（AUC = 0.68; 95％CI） = 0.59–0.76）。但是，mtDNA只能将癌症与对照区分开（AUC = 0.65； 95％CI = 0.56-0.73）。较高的nDNA水平还与癌症患者的死亡率增加相关（危险比= 2.3； 95％CI = 1.1-4.7）。循环中的无细胞nDNA而非mtDNA可以将多种癌症与非恶性疾病区分开，并且与癌症患者的不良生存率相关。