背景：在西方国家，乳腺癌（BC）是女性最常见的癌症。早期发现对生存有积极影响，生活质量,和公共卫生费用。乳房X光检查筛查计划提高了早期检出率，但是更个性化监测的新方法可以进一步改善诊断。血液中循环的无细胞DNA（cfDNA）可以通过分析cfDNA数量为早期诊断提供潜在的工具，循环肿瘤DNA突变，或cfDNA完整性(cfDI)。
方法：从106例乳腺癌患者（病例）和103例健康女性（对照）的血液中获得血浆。数字液滴PCR用于测定ALU260/111bp和LINE-1266/97bp拷贝数比和cfDI。使用EEF1A2基因的拷贝计算cfDNA丰度。用受试者工作特征曲线(ROC)分析生物标志物鉴别的准确性。进行了敏感性分析，以将年龄解释为潜在的混杂因素。
结果：病例的ALU260/111或LINE-1266/97拷贝数比率显着降低（中位数；ALU260/111=0.08，LINE-1266/97=0.20），与对照组相比（中位数；ALU260/111=0.10，LINE-1266/97=0.28）（p<0.001）。ROC分析表明，拷贝数比将病例与对照组区分开（曲线下面积，AUC=0.69，95%CI：ALU为0.62-0.76，LINE-1为0.80，95%CI：0.73-0.86）。来自cfDI的ROC证实了LINE-1与ALU相比具有更好的诊断性能。
结论：通过ddPCR分析LINE-1266/97拷贝数比或cfDI似乎是一种有用的非侵入性测试，可以帮助早期BC检测。需要在大型队列中进行进一步的研究来验证生物标志物。
BACKGROUND: In Western countries, breast cancer (BC) is the most common cancer in women. Early detection has a positive impact on survival, quality of life, and public health costs. Mammography screening programs have increased early detection rates, but new approaches to more personalized surveillance could further improve diagnosis. Circulating cell-free DNA (cfDNA) in blood could provide a potential tool for early diagnosis by analyzing cfDNA quantity, circulating tumor DNA mutations, or cfDNA integrity (cfDI).
METHODS: Plasma was obtained from the blood of 106 breast cancer patients (cases) and 103 healthy women (controls). Digital droplet PCR was used for the determination of
ALU 260/111 bp and LINE-1 266/97 bp copy number ratio and cfDI. cfDNA abundance was calculated using copies of the EEF1A2 gene. The accuracy of biomarker discrimination was analyzed with receiver operating characteristic curve (ROC). Sensitivity analyses were performed to account for age as a potential confounder.
RESULTS: Cases had significantly lower
ALU 260/111 or LINE-1 266/97 copy number ratios (median;
ALU 260/111 = 0.08, LINE-1 266/97 = 0.20), compared with control (median;
ALU 260/111 = 0.10, LINE-1 266/97 = 0.28) (p < 0.001). ROC analysis showed that copy number ratio discriminated cases from controls (area under the curve, AUC = 0.69, 95% CI: 0.62-0.76 for
ALU and 0.80, 95% CI: 0.73-0.86 for LINE-1). ROC from cfDI confirmed the better diagnostic performance of LINE-1 compared with
ALU.
CONCLUSIONS: Analysis of LINE-1 266/97 copy number ratio or cfDI by ddPCR appears to be a useful noninvasive test that could aid in early BC detection. Further studies in a large cohort are needed to validate the biomarker.
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