Division of Molecular Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
Cancer Biomark. 2020;28(2):159-167. doi: 10.3233/CBM-191018.
Minimal invasive blood-based molecular markers are evaluated as promising biomarkers in malignant diseases these days.
In this pilot study, we investigated the potential of cell-free DNA (cfDNA) concentration and cell-free DNA Integrity (cfDI) as blood-based diagnostic markers for ovarian cancer patients in a retrospective study cohort.
cfDNA concentration and cfDI were determined in the plasma of 37 ovarian cancer patients and 28 healthy controls, by measuring ALU and LINE1 repetitive DNA elements using quantitative real-time PCR.
A high correlation was observed between the results of ALU and LINE1. The correlated co-efficiency between the values of cfDNA concentration and cfDI was 0.86 and 0.71. As for the results between cases and controls, no or just borderline significant difference was observed in cfDI after age adjustment (P= 0.40 for ALU and P= 0.05 for LINE1) while cfDNA concentration showed a significant difference between ovarian cancer patients and healthy controls groups (P= 0.03 for ALU and P= 3.00 E-03 for LINE1). cfDNA concentration of ALU and LINE1 had an AUC of 0.81 (0.70-0.91). ALU and LINE1 cfDI reached an AUC of 0.60 (95% CI: 0.46-0.73). The combination of these markers reached the best diagnostic power with an AUC of 0.84.
cfDNA variables might be potentially diagnostic biomarkers in ovarian cancer, in combination with additional molecular markers. However, further studies are needed to confirm the diagnostic ability of cfDNA variables (cfDNA concentration and cfDI).
微创血液分子标志物目前被评估为恶性疾病有前途的生物标志物。
在这项初步研究中，我们通过使用定量实时 PCR 测量 ALU 和 LINE1 重复 DNA 元件，在回顾性研究队列中研究了游离 DNA (cfDNA) 浓度和游离 DNA 完整性 (cfDI) 作为卵巢癌患者血液诊断标志物的潜力。
通过定量实时 PCR 测量 ALU 和 LINE1 重复 DNA 元件，在 37 例卵巢癌患者和 28 例健康对照者的血浆中测定 cfDNA 浓度和 cfDI。
ALU 和 LINE1 的结果之间观察到高度相关性。cfDNA 浓度和 cfDI 的相关系数分别为 0.86 和 0.71。就病例和对照组的结果而言，在调整年龄后，cfDI 没有或仅有边缘显著差异（ALU 的 P=0.40，LINE1 的 P=0.05），而 cfDNA 浓度在卵巢癌患者和健康对照组之间存在显著差异（ALU 的 P=0.03，LINE1 的 P=3.00E-03）。ALU 和 LINE1 的 cfDNA 浓度 AUC 为 0.81（0.70-0.91）。ALU 和 LINE1 的 cfDI 达到 AUC 为 0.60（95%CI：0.46-0.73）。这些标志物的组合具有最佳的诊断效能，AUC 为 0.84。
cfDNA 变量可能是卵巢癌的潜在诊断生物标志物，与其他分子标志物结合使用。然而，需要进一步的研究来确认 cfDNA 变量（cfDNA 浓度和 cfDI）的诊断能力。
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