Using plasma cell-free DNA to monitor the chemoradiotherapy course of cervical cancer
Using plasma cell-free DNA to monitor the chemoradiotherapy course of cervical cancer
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利用血浆游离DNA监测宫颈癌放化疗过程
DOI：
10.1002/ijc.32295
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发表时间：
2019-11-01
影响因子：
6.4
通讯作者：
Li, Zhiguang
中科院分区：
文献类型：
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作者：
Tian, Jichao;Geng, Yan;Li, Zhiguang
液体活组织检查正被纳入癌症诊断和监测。然而，关键问题仍然存在，例如如何精确评估癌症突变负荷并解释相应的临床意义。在此，我们评估了外周血游离DNA（cfDNA）在表征来自宫颈癌患者的48个癌症驱动基因的动态突变改变中的作用。我们对来自57名宫颈癌患者的93份血浆cfDNA进行了靶向深度测序，并由此开发了一种算法，等位基因分数偏差（AFD），以无偏的方式监测基因组畸变的动态变化。不同的治疗，包括化疗（n = 22），放疗（n = 14）和手术（n = 15），导致AFD值显著降低（Wilcoxon，p = 0.029）。在大多数患者中，cfDNA AFD值的降低伴随着肿瘤大小的缩小。然而，在cfDNA AFD值不反映肿瘤大小减小的患者亚组中，检测到进行性疾病（转移）。此外，诊断时AFD值较低，随后AFD值增加也成功预测复发。这些结果表明，血浆cfDNA与靶向深度测序一起可能有助于预测宫颈癌的治疗反应和疾病发展。
The liquid biopsy is being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and interpret the corresponding clinical implications. Herein, we evaluated the role of peripheral blood cell-free DNA (cfDNA) in characterizing the dynamic mutation alterations of 48 cancer driver genes from cervical cancer patients. We performed targeted deep sequencing on 93 plasma cfDNA from 57 cervical cancer patients and from this developed an algorithm, allele fraction deviation (AFD), to monitor in an unbiased manner the dynamic changes of genomic aberrations. Differing treatments, including chemotherapy (n = 22), radiotherapy (n = 14) and surgery (n = 15), led to a significant decrease in AFD values (Wilcoxon, p = 0.029). The decrease of cfDNA AFD values was accompanied by shrinkage in the size of the tumor in most patients. However, in a subgroup of patients where cfDNA AFD values did not reflect a reduction in tumor size, there was a detection of progressive disease (metastasis). Furthermore, a low AFD value at diagnosis followed a later increase of AFD value also successfully predicted relapse. These results show that plasma cfDNA, together with targeted deep sequencing, may help predict treatment response and disease development in cervical cancer.