放化疗食管癌患者心肌细胞特异性循环无细胞甲基化DNA

IF 0.9 Q4 GASTROENTEROLOGY & HEPATOLOGY
S. Roth, E. Vietsch, Megan E. Barefoot, Marcel O. Schmidt, Matthew D. Park, Archana Ramesh, Michael R. Lindberg, G. Giaccone, A. Riegel, A. Barac, K. Unger, A. Wellstein
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引用次数: 2

摘要

胸部高剂量放射治疗癌症与早期和晚期心脏毒性有关。为了评估RT引起的心肌细胞死亡率的改变,我们监测了进入循环的心肌细胞特异性、无细胞甲基化DNA (cfDNA)的变化。11例远端食管癌患者接受50.4 Gy (RT)的新辅助放化疗,同时使用卡铂和紫杉醇。受试者在RT开始前、完成后以及RT后4-6个月进行空腹抽血。FAM101A位点上的6个未甲基化CpGs岛用于鉴定血清中心肌细胞特异性cfDNA。亚硫酸氢盐处理后,该特异性cfDNA通过扩增子测序在>35,000 reads/分子的深度进行定量。在大多数患者样本中,心肌细胞特异性cfDNA在RT前可检测到,并在治疗和恢复过程中显示出一些明显的变化。我们认为,虽然合并症可能会掩盖治疗特异性事件,但这些变化表明患者对治疗的特异性心脏损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cardiomyocyte-specific circulating cell-free methylated DNA in esophageal cancer patients treated with chemoradiation
Thoracic high dose radiation therapy (RT) for cancer has been associated with early and late cardiac toxicity. To assess altered rates of cardiomyocyte cell death due to RT we monitored changes in cardiomyocyte-specific, cell-free methylated DNA (cfDNA) shed into the circulation. Eleven patients with distal esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy (RT) and concurrent carboplatin and paclitaxel were enrolled. Subjects underwent fasting blood draws prior to the initiation and after completion of RT as well as 4–6 months following RT. An island of six unmethylated CpGs in the FAM101A locus was used to identify cardiomyocyte-specific cfDNA in serum. After bisulfite treatment this specific cfDNA was quantified by amplicon sequencing at a depth of >35,000 reads/molecule. Cardiomyocyte-specific cfDNA was detectable before RT in the majority of patient samples and showed some distinct changes during the course of treatment and recovery. We propose that patient-specific cardiac damages in response to the treatment are indicated by these changes although co-morbidities may obscure treatment-specific events.
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来源期刊
CiteScore
1.50
自引率
0.00%
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审稿时长
10 weeks
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