Cell-Free Circulating DNA: Diagnostic Value in Patients With Testicular Germ Cell Cancer
Cell-Free Circulating DNA: Diagnostic Value in Patients With Testicular Germ Cell Cancer
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DOI：
10.1016/j.juro.2008.08.118
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发表时间：
2009-01-01
影响因子：
6.6
通讯作者：
Bastian, Patrick J.
中科院分区：
文献类型：
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作者：
Ellinger, Joerg;Wittkarnp, Volker;Bastian, Patrick J.
目的：在各种恶性肿瘤中，无细胞循环DNA水平的增加被描述为诊断和预后的生物标志物。材料与方法：从74例睾丸癌患者血清中提取游离DNA，其中睾丸癌组39例，非睾丸癌组35例，正常对照组35例。实时聚合酶链反应被用来定量的106，193和384肌动蛋白-P的DNA片段。DNA完整性表示为大（193或384 bp）与短（106 bp）DNA fragments.Results的比率：与健康个体相比，癌症患者中的肌动蛋白-β-106/193/384片段水平显著增加（每个p < 0.001）。癌症患者的DNA完整性显著降低（p < 0.001）。当比较非腺瘤和腺瘤患者时，游离DNA片段水平无差异（p > 0.24）。ROC分析表明，游离DNA水平以87%的灵敏度和97%的特异性区分癌症患者和健康个体。即使在31例患者中，其中已建立的血清肿瘤标志物甲胎蛋白，人绒毛膜促性腺激素，胎盘碱性磷酸酶和乳酸脱氢酶是正常的细胞游离DNA水平，使我们能够区分癌症患者和健康人之间的敏感性为84%，特异性为97%。临床3期患者的游离DNA水平比1期或2期患者更频繁地升高（p < 0.046）。结论：睾丸癌患者的游离DNA水平升高，它们可以准确区分健康个体。无细胞DNA的高灵敏度可以促进睾丸癌的管理，特别是在常规肿瘤标志物未增加的患者中。
Purpose: Increased levels of cell-free circulating DNA have been described in various malignancies as a diagnostic and prognostic biormarker. We analyzed the significance of cell-free DNA in patients with testicular cancer.Materials and Methods: Cell-free DNA was isolated from the serum of 74 patients with testicular cancer, including 39 with seminoma and 35 with nonseminoma, and 35 healthy individuals. Real-time polymerase chain reaction was used to quantify a 106, a 193 and a 384 actin-P DNA fragment. DNA integrity is expressed as the ratio of large (193 or 384 bp) to short (106 bp) DNA fragments.Results: Actin-beta-106/193/384 fragment levels were significantly increased in patients with cancer compared to those in healthy individuals (each p < 0.001). DNA integrity was significantly decreased in patients with cancer (p < 0.001). Cell-free DNA fragment levels were not different when comparing patients with nonseminoma and seminoma (p > 0.24). ROC analysis demonstrated that cell-free DNA levels distinguished patients with cancer from healthy individuals with 87% sensitivity and 97% specificity. Even in 31 patients in whom the established serum tumor markers a-fetoprotein, human chorionic gonadotropin, placental alkaline phosphatase and lactate dehydrogenase were normal cell-free DNA levels allowed us to distinguish between patients with cancer and healthy individuals with 84% sensitivity and 97% specificity. Cell-free DNA levels were more frequently increased in patients with clinical stage 3 than in patients with stage 1 or 2 disease (p < 0.046).Conclusions: Cell-free DNA levels are increased in patients with testicular cancer and they allow the accurate discrimination of healthy individuals. The high sensitivity of cell-free DNA could facilitate the management of testicular cancer, especially in patients with conventional tumor markers that are not increased.