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在局部晚期乳腺癌患者中,化疗前后血浆总 cfDNA 水平的鉴定可作为新辅助化疗反应的指标。

Identification of the plasma total cfDNA level before and after chemotherapy as an indicator of the neoadjuvant chemotherapy response in locally advanced breast cancer.

机构信息

Department of Breast Surgery, The Firsft Affiliated Hospital with Nanjing Medical University, Nanjing, China.

Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

Cancer Med. 2020 Apr;9(7):2271-2282. doi: 10.1002/cam4.2906. Epub 2020 Feb 3.

Abstract

This study aimed to retrospectively evaluate the circulating free DNA (cfDNA) level in patients with locally advanced breast cancer (LABC) having different neoadjuvant chemotherapy (NCT) responses and to investigate whether dynamic changes in cfDNA level could predict the effectiveness of NCT in patients with LABC. Data on 61 patients with LABC were included. NCT responses were evaluated using the response evaluation criteria. Blood samples were collected for cfDNA detection before treatment and after the first and eighth courses of chemotherapy. The Alu 111-bp and 260-bp fragment levels were evaluated by polymerase chain reaction, and the predictive value of the cfDNA level in the NCT response was determined. In vitro, the MCF-7 and MCF-7/ADR cell lines were applied to simulate the phenomenon of drug resistance and explain the underlying mechanism. The Alu 111-bp level increased after the first NCT course (P = .014) and then remained high after NCT in the high-R group (P = .047), but it remained steady in the low-R group during NCT. A similar tendency in the Alu 260-bp level was revealed in different groups. The ∆∆Ct value of Alu 260-bp had good diagnostic efficiency in assessing predictive ability. The area under the curve for the ∆∆Ct1 and ∆∆Ct2 of Alu 260-bp was 0.697 and 0.647, respectively. The cfDNA level was closely related to epirubicin-induced apoptosis and changes in the Ki-67 index in vitro. The elevation of cfDNA after one chemotherapy cycle was mediated by the apoptosis of tumor cells and related to the improved chemotherapy response.

摘要

本研究旨在回顾性评估不同新辅助化疗(NCT)反应的局部晚期乳腺癌(LABC)患者的循环游离 DNA(cfDNA)水平,并探讨 cfDNA 水平的动态变化是否可以预测 LABC 患者 NCT 的疗效。纳入了 61 例 LABC 患者。使用反应评估标准评估 NCT 反应。在治疗前和化疗第 1 及第 8 疗程后采集血液样本进行 cfDNA 检测。通过聚合酶链反应评估 Alu 111-bp 和 260-bp 片段水平,并确定 cfDNA 水平在 NCT 反应中的预测价值。在体外,应用 MCF-7 和 MCF-7/ADR 细胞系模拟耐药现象并解释其潜在机制。Alu 111-bp 水平在第 1 个 NCT 疗程后升高(P =.014),然后在高 R 组的 NCT 后仍保持高水平(P =.047),但在低 R 组的 NCT 期间保持稳定。不同组中 Alu 260-bp 水平也显示出类似的趋势。Alu 260-bp 的 ∆∆Ct 值在评估预测能力方面具有良好的诊断效率。Alu 260-bp 的 ∆∆Ct1 和 ∆∆Ct2 的曲线下面积分别为 0.697 和 0.647。cfDNA 水平与表阿霉素诱导的细胞凋亡和 Ki-67 指数的变化密切相关。一个化疗周期后 cfDNA 的升高是由肿瘤细胞的凋亡介导的,与化疗反应的改善有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24d5/7131846/19979640ca2e/CAM4-9-2271-g001.jpg

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