Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients
Analysis of ctDNA to predict prognosis and monitor treatment responses in metastatic pancreatic cancer patients
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DOI：
10.1002/ijc.30650
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发表时间：
2017-05-15
影响因子：
6.4
通讯作者：
Yu, Xianjun
中科院分区：
文献类型：
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作者：
Cheng, He;Liu, Chen;Yu, Xianjun
血浆中游离循环肿瘤DNA （ctDNA）已被用作多种肿瘤的潜在无创生物标志物。我们的研究是为了评估ctDNA检测在转移性胰腺癌患者中的临床意义。首先，我们试图通过外显子组测序对10例转移性胰腺癌患者的游离DNA （cfDNA）中的60个基因进行前瞻性筛选。其次，采用液滴数字PCR （ddPCR）技术鉴定188例转移性胰腺癌患者的潜在突变。最后，为了初步评估ctDNA在监测化疗后肿瘤反应中的潜在作用，我们在13例转移性胰腺癌患者的一系列血浆样本中检测了ctDNA的存在（临床试验：NCT02017015）。分析显示在BRCA2、EGFR、KDR和ERBB2基因位点上有5个体细胞突变。BRCA2、KDR、EGFR、ERBB2外显子17和ERBB2外显子27的ctDNA突变频率分别为11.7%、13.8%、13.3%、13.3%和6.4%。单因素和多因素分析发现，ERBB2外显子17突变（p=0.035， HR=1.61）是与转移性胰腺癌患者总生存率相关的独立因素。此外，CT成像评估的ctDNA检出率和治疗反应的一致性为76.9%（13例中有10例），ctDNA的存在为10例患者中的6例（60%）提供了最早的治疗措施。ctDNA测序可能在确定转移性胰腺癌治疗和监测肿瘤反应方面具有临床价值。有什么新鲜事吗?我们在BRCA2、EGFR、KDR和ERBB2基因位点发现了5个体细胞突变。ctDNA中ERBB2外显子17突变被认为是一个独立的预后因素。此外，ctDNA的存在与肿瘤反应相关，并为10名患者中的6名（60%）提供了最早的治疗措施。检测ctDNA突变可用于指导治疗决策，并监测转移性胰腺癌患者的治疗反应。
Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. Our study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. First, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Second, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer. Finally, to preliminary evaluate the potential role of ctDNA in monitoring tumor responses following chemotherapy, we detected the presence of ctDNA in serial plasma samples from 13 metastatic pancreatic cancer patients (Clinical trial: NCT02017015). The analysis revealed five somatic mutations at BRCA2, EGFR, KDR and ERBB2 gene loci. The frequencies of ctDNA mutation at BRCA2, KDR, EGFR, ERBB2 exon17 and ERBB2 exon27 were 11.7%, 13.8%, 13.3%, 13.3% and 6.4% respectively. Univariate and multivariate analyses identified the ERBB2 exon17 mutation (p=0.035, HR=1.61) as an independent factor associated with overall survival among metastatic pancreatic cancer patients. Furthermore, the rate of coincident detection of ctDNA and response to treatment as assessed by CT imaging was 76.9% (10 of 13 cases), and the presence of ctDNA provided the earliest measure of treatment in 6 of 10 patients (60%). ctDNA sequencing may have clinical value for determining metastatic pancreatic cancer treatment and monitoring the tumor response.What's new? We identified five somatic mutations at BRCA2, EGFR, KDR and ERBB2 gene loci. ERBB2 exon17 mutation in ctDNA was identified as an independent prognostic factor. In addition, the presence of ctDNA was associated with tumor responses, and provided the earliest measure of treatment in 6 of 10 patients (60%). Detection of ctDNA mutation may be used to guide treatment decisions, and monitor treatment responses in metastatic pancreatic cancer patients.