Maltoni Roberta, Casadio Valentina, Ravaioli Sara, Foca Flavia, Tumedei Maria Maddalena, Salvi Samanta, Martignano Filippo, Calistri Daniele, Rocca Andrea, Schirone Alessio, Amadori Dino, Bravaccini Sara
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Oncotarget. 2017 Mar 7;8(10):16642-16649. doi: 10.18632/oncotarget.15120.
As conventional biomarkers for defining breast cancer (BC) subtypes are not always capable of predicting prognosis, search for new biomarkers which can be easily detected by liquid biopsy is ongoing. It has long been known that cell-free DNA (CF-DNA) could be a promising diagnostic and prognostic marker in different tumor types, although its prognostic value in BC is yet to be confirmed. This retrospective study evaluated the prognostic role of CF-DNA quantity and integrity of HER2, MYC, BCAS1 and PI3KCA, which are frequently altered in BC. We collected 79 serum samples before surgery from women at first diagnosis of BC at Forlì Hospital (Italy) from 2002 to 2010. Twenty-one relapsed and 58 non-relapsed patients were matched by subtype and age. Blood samples were also collected from 10 healthy donors. All samples were analyzed by Real Time PCR for CF-DNA quantity and integrity of all oncogenes. Except for MYC, BC patients showed significantly higher median values of CF-DNA quantity (ng) than healthy controls, who had higher integrity and lower apoptotic index. A difference nearing statistical significance was observed for HER2 short CF-DNA (p = 0.078, AUC value: 0.6305). HER2 short CF-DNA showed an odds ratio of 1.39 for disease recurrence with p = 0.056 (95% CI 0.991-1.973). Our study suggests that CF-DNA detected as liquid biopsy could have great potential in clinical practice once demonstration of its clinical validity and utility has been provided by prospective studies with robust assays.
由于用于定义乳腺癌（BC）亚型的传统生物标志物并不总是能够预测预后，因此人们正在寻找能够通过液体活检轻松检测到的新生物标志物。长期以来，已知游离DNA（CF-DNA）可能是不同肿瘤类型中有前景的诊断和预后标志物，尽管其在BC中的预后价值尚未得到证实。这项回顾性研究评估了CF-DNA数量以及HER2、MYC、BCAS1和PI3KCA完整性的预后作用，这些基因在BC中经常发生改变。我们收集了2002年至2010年期间在意大利弗利医院首次诊断为BC的女性患者术前的79份血清样本。根据亚型和年龄匹配了21例复发患者和58例未复发患者。还从10名健康供体中采集了血样。所有样本均通过实时PCR分析CF-DNA数量以及所有癌基因的完整性。除MYC外，BC患者的CF-DNA数量（ng）中位数显著高于健康对照，健康对照具有更高的完整性和更低的凋亡指数。HER2短CF-DNA观察到接近统计学意义的差异（p = 0.078，AUC值：0.6305）。HER2短CF-DNA显示疾病复发的优势比为1.39，p = 0.056（95% CI 0.991-1.973）。我们的研究表明，一旦通过具有可靠检测方法的前瞻性研究证明其临床有效性和实用性，作为液体活检检测到的CF-DNA在临床实践中可能具有巨大潜力。
