Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid.

Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid.
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DOI:
10.1002/cjp2.207
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发表时间:
2021-05
期刊:
The journal of pathology. Clinical research
影响因子:
--
通讯作者:
Fijneman RJ
Fijneman RJ
中科院分区:
其他
文献类型:
--
作者:
Van't Erve I;Rovers KP;Constantinides A;Bolhuis K;Wassenaar EC;Lurvink RJ;Huysentruyt CJ;Snaebjornsson P;Boerma D;van den Broek D;Buffart TE;Lahaye MJ;Aalbers AG;Kok NF;Meijer GA;Punt CJ;Kranenburg O;de Hingh IH;Fijneman RJ

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肿瘤源性无细胞 DNA (cfDNA) 是一种新兴的生物标志物,用于指导转移性结直肠癌 (CRC) 患者的个性化治疗。虽然 CRC 肝转移 (CRC-LM) 患者的血浆 cfDNA 水平相对较高,但人们对 CRC 腹膜转移 (CRC-PM) 患者知之甚少。本研究评估了 20 名孤立性 CRC-PM 患者的血浆和腹膜液(即腹水或腹膜冲洗液)和 100 名孤立性 CRC-LM 患者血浆中肿瘤源性 cfDNA 的存在情况。在肿瘤组织 KRAS/BRAF 突变携带者中,通过液滴数字聚合酶链反应 (ddPCR) 在 93% CRC-LM 和 20% CRC-PM 患者的血浆中以及在所有 CRC-PM 患者的腹膜液中检测到肿瘤源性 cfDNA。 CRC-PM 血浆中的突变等位基因分数 (MAF) 和每毫升突变拷贝数 (MTc/ml) 低于 CRC-LM 血浆(中位 MAF = 0.28 对比 18.9%,p < 0.0001;中位 MTc/ml = 21 对比 1,758,p < 0.0001)。在 CRC-PM 患者中,腹腔液中的 cfDNA 水平高于血浆(中位 MAF = 16.4 与 0.28%,p = 0.0019;中位 MTc/ml = 305 与 21,p = 0.0034)。这些数据表明血浆中肿瘤来源的 cfDNA 是监测 CRC-PM 的不良生物标志物。相反,腹膜液中的 cfDNA 检测可能提供一种替代方案来指导 CRC-PM 治疗决策。
Tumor‐derived cell‐free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While patients with CRC liver metastases (CRC‐LM) have relatively high levels of plasma cfDNA, little is known about patients with CRC peritoneal metastases (CRC‐PM). This study evaluated the presence of tumor‐derived cfDNA in plasma and peritoneal fluid (i.e. ascites or peritoneal washing) in 20 patients with isolated CRC‐PM and in the plasma of 100 patients with isolated CRC‐LM. Among tumor tissue KRAS/BRAF mutation carriers, tumor‐derived cfDNA was detected by droplet digital polymerase chain reaction (ddPCR) in plasma of 93% of CRC‐LM and 20% of CRC‐PM patients and in peritoneal fluid in all CRC‐PM patients. Mutant allele fraction (MAF) and mutant copies per ml (MTc/ml) were lower in CRC‐PM plasma than in CRC‐LM plasma (median MAF = 0.28 versus 18.9%, p < 0.0001; median MTc/ml = 21 versus 1,758, p < 0.0001). Within patients with CRC‐PM, higher cfDNA levels were observed in peritoneal fluid than in plasma (median MAF = 16.4 versus 0.28%, p = 0.0019; median MTc/ml = 305 versus 21, p = 0.0034). These data imply that tumor‐derived cfDNA in plasma is a poor biomarker to monitor CRC‐PM. Instead, cfDNA detection in peritoneal fluid may offer an alternative to guide CRC‐PM treatment decisions.
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影响因子: 16.6
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