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监测循环肿瘤DNA发现转移性结直肠癌患者的状态呈动态变化。

Monitoring circulating tumor DNA revealed dynamic changes in status in patients with metastatic colorectal cancer.

作者信息

Takayama Yuji, Suzuki Koichi, Muto Yuta, Ichida Kosuke, Fukui Taro, Kakizawa Nao, Ishikawa Hideki, Watanabe Fumiaki, Hasegawa Fumi, Saito Masaaki, Tsujinaka Shingo, Futsuhara Kazushige, Miyakura Yasuyuki, Noda Hiroshi, Konishi Fumio, Rikiyama Toshiki

机构信息

Department of Surgery, Saitama Medical Center, Jichi Medical University, Omiya-ku, Saitama 330-8503, Japan.

Department of Surgery, Nerima-Hikarigaoka Hospital, Nerima-ku, Tokyo 179-0072, Japan.

出版信息

Oncotarget. 2018 May 11;9(36):24398-24413. doi: 10.18632/oncotarget.25309.

Abstract

mutated circulating tumor DNA (MctDNA) can be monitored in the blood of patients with metastatic colorectal cancer (mCRC), but dynamic changes have not been determined. Four hundred and fifty-seven plasma samples were collected prospectively from 85 mCRC patients who underwent chemotherapy. MctDNA in plasma was detected by droplet digital PCR, and the percentage of MctDNA in total circulating cell-free DNA was calculated. assessment in tumor tissues showed 29 patients with the mutant-type (MT) and 56 patients with the wild-type (WT). Twenty-three of 29 MT patients (79.3%) and 28 of 56 WT patients (50.0%) showed MctDNA. Emergence of MctDNA was recognized during treatments with various drugs. Regardless of status in tumor tissues, patients with MctDNA in blood showed poor progression-free survival with first-line treatment. Median percentage of MctDNA accounted for 10.10% in MT patients and 0.22% in WT patients. These differences between MT and WT likely affected patterns of changes in MctDNA. monitoring identified dynamic changes in MctDNA, such as continuous, intermittent, and transient changes (quick elevation and disappearance). Emergence of MctDNA involved drug resistance, except for transient changes, which were seen in WT patients and likely corresponded with the drug response. Transient changes could be involved in recovery of sensitivity to anti-EGFR antibody in WT patients. Monitoring MctDNA during various treatments showed dynamic changes in status and could provide useful information for determining treatments for patients with mCRC.

摘要

转移性结直肠癌(mCRC)患者血液中可监测到突变循环肿瘤DNA(MctDNA),但其动态变化尚未明确。前瞻性收集了85例接受化疗的mCRC患者的457份血浆样本。采用液滴数字PCR检测血浆中的MctDNA,并计算MctDNA在总循环游离DNA中的百分比。肿瘤组织评估显示,29例为突变型(MT),56例为野生型(WT)。29例MT患者中有23例(79.3%)和56例WT患者中有28例(50.0%)检测到MctDNA。在使用各种药物治疗期间可识别出MctDNA的出现。无论肿瘤组织状态如何,血液中存在MctDNA的患者一线治疗的无进展生存期较差。MT患者中MctDNA的中位百分比为10.10%,WT患者为0.22%。MT和WT之间的这些差异可能影响了MctDNA的变化模式。监测发现MctDNA存在动态变化,如持续、间歇和短暂变化(快速升高和消失)。MctDNA的出现与耐药性有关,短暂变化除外,短暂变化见于WT患者,可能与药物反应相关。短暂变化可能与WT患者对抗表皮生长因子受体(EGFR)抗体的敏感性恢复有关。在各种治疗过程中监测MctDNA显示其状态存在动态变化,可为确定mCRC患者的治疗提供有用信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eade/5966256/8c9fd857c4fe/oncotarget-09-24398-g001.jpg

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