Thyroid cancer is the most common endocrine malignancy, and its incidence continues to rise. For clinicians with cancer patients, choosing and interpreting diagnostic laboratory studies has become increasingly important. Previously, changes in plasma free mitochondrial DNA levels have been found in colorectal, breast, lung, and urinary cancers, and have demonstrated diagnostic value. In this study, we investigated whether the occurrence and development of thyroid cancer might be predicted using mtDNA copy number (ND1), mtDNA integrity (ND4/ND1) and levels of cell-free nDNA (GAPDH). We analyzed ND1, ND4, and GAPDH levels in plasma and blood cells from 75 patients with thyroid cancer, 40 patients with nodular goiter, and 107 normal controls using real-time PCR. Although both the thyroid nodule and thyroid cancer patients had significantly increased ND1 levels, the ND4/ND1 ratio in the thyroid cancer group was higher than the thyroid nodule group (P< 0.05), and significantly higher than the normal control group (P<0.01). Plasma levels of nuclear DNA (GAPDH) in the thyroid cancer group were also higher compared to normal (P< 0.05). These results indicate that increased intactness of plasma free mtDNA is associated with increased levels of plasma cell-free nDNA, and that the ND4/ND1 ratio has the potential to be a new detection indicator in thyroid cancer. Furthermore, we classified thyroid cancer patients according to clinical data including age, tumor size, and metastasis. We found significantly higher levels of GAPDH in malignant tissues. Because ND4/ND1 correlated with plasma GAPDH in the plasma studies, this also suggests a potential relationship between ND4 intactness and thyroid tumor tissue size. Taken together, our findings suggest a tumor-specific process involving increased release of intact mtDNA, detectable in the plasma, which differentiates normal patients from patients with thyroid cancer.

中文翻译：

---

循环游离线粒体DNA对疑似甲状腺癌患者的诊断价值：ND4/ND1比值作为新的潜在血浆标志物


甲状腺癌是最常见的内分泌恶性肿瘤，且发病率持续上升。对于癌症患者的临床医生来说，选择和解释诊断实验室研究变得越来越重要。此前，在结直肠癌、乳腺癌、肺癌和泌尿系癌症中发现了血浆游离线粒体DNA水平的变化，并已证明了诊断价值。在本研究中，我们研究了是否可以使用 mtDNA 拷贝数 (ND1)、mtDNA 完整性 (ND4/ND1) 和游离 nDNA (GAPDH) 水平来预测甲状腺癌的发生和发展。我们使用实时 PCR 分析了 75 名甲状腺癌患者、40 名结节性甲状腺肿患者和 107 名正常对照者血浆和血细胞中的 ND1、ND4 和 GAPDH 水平。虽然甲状腺结节和甲状腺癌患者ND1水平均显着升高，但甲状腺癌组ND4/ND1比值高于甲状腺结节组（P<<0.05），且显着高于正常对照组（P% 3C0.01）。甲状腺癌组的血浆核DNA（GAPDH）水平也高于正常组（P< 0.05）。这些结果表明，血浆游离mtDNA完整性的增加与血浆游离nDNA水平的增加有关，ND4/ND1比值有可能成为甲状腺癌的新检测指标。此外，我们根据年龄、肿瘤大小和转移等临床数据对甲状腺癌患者进行分类。我们发现恶性组织中 GAPDH 水平显着升高。由于血浆研究中 ND4/ND1 与血浆 GAPDH 相关，因此这也表明 ND4 完整性与甲状腺肿瘤组织大小之间存在潜在关系。 总而言之，我们的研究结果表明，肿瘤特异性过程涉及血浆中可检测到的完整线粒体DNA释放增加，这将正常患者与甲状腺癌患者区分开来。