Methylated ctDNA Quantification: Noninvasive Approach to Monitoring Hepatocellular Carcinoma Burden.
Methylated ctDNA Quantification: Noninvasive Approach to Monitoring Hepatocellular Carcinoma Burden.
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甲基化 ctDNA 定量：监测肝细胞癌负担的无创方法。
DOI：
10.1097/xcs.0000000000000939
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发表时间：
2024
影响因子：
5.2
通讯作者：
Zarrinpar,Ali
中科院分区：
文献类型：
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作者：
Angeli-Pahim,Isabella;Chambers,Anastasia;Duarte,Sergio;Soma,Daiki;Beduschi,Thiago;Sahin,Ilyas;Hughes,Steven;Zarrinpar,Ali
背景：对肝细胞癌治疗效果的非侵入性、精确监测将极大地促进个体化治疗和改善患者预后。我们假设，定量甲基化循环肿瘤DNA(CtDNA)可以在不需要活检的情况下有效地监测肝细胞癌的负担。研究设计：在一个高容量的学术医学中心，在整个治疗过程中的不同时间点采集了25例患者的血样，其中21例为肝癌，4例为良性肝肿块。甲基化ctDNA分子的量化评估了550多个预先选择的癌症特异性扩增片段上的CpG位点。结果：在10例肝细胞癌手术患者(手术切除5例，肝移植5例)中，9例术后甲基化评分显著下降。1例≤持续升高的患者随后被发现有转移性疾病。阴性对照队列中的患者在手术前和手术后均有正常范围的TMS。术前TMS与手术标本的肿瘤负担呈中度相关(Spearman r=0.54)。对11例接受全身治疗或Y90放射栓塞术的受试者的16个时间段的分析表明，与Δ[曲线下面积(AUC值)分别为0.800和0.783]相比，TM(AUCTM)的变化与肿瘤进展的相关性更好。Δ曲线下面积(AUCAUC值分别为0.800和0.783)。Δ甲基化评分与Δ甲基化评分相结合进一步提高了检测肿瘤进展的能力，AUC值为0.892。结论：CTDNA甲基化评分可以有效地评估肿瘤负荷的变化，而不需要肿瘤活检。
Background:Non-invasive, precision monitoring of hepatocellular carcinoma (HCC) treatment efficacy would greatly facilitate personalized therapy and improve patient outcomes. We hypothesize that quantifying methylated circulating tumor DNA (ctDNA) can be used to effectively monitor HCC burden without the need for biopsy.Study Design:Blood samples were collected from 25 patients, 21 with HCC and 4 with benign liver masses, at various timepoints throughout the course of treatment at a high-volume academic medical center. Quantification of methylated ctDNA molecules assessed CpG sites on over 550 preselected cancer-specific amplicons. The Tumor Methylation Score (TMS) was calculated by measuring the difference between the amount of methylation in the plasma and buffy coat with a normal cutoff of≤ 120.Results:Among 10 surgical HCC patients (5 surgical resections and 5 liver transplants), TMS revealed a statistically significant, rapid postoperative decline in 9. One patient who had a persistently elevated TMS on POD1 was subsequently found to have had metastatic disease. Patients in the negative control cohort all had normal-range pre-and post-operative TMS. Pre-operative TMS correlated moderately with tumor burden on pathology (Spearman r= 0.54) of surgical specimens. From 11 subjects undergoing systemic therapy or Y90 radioembolization, analysis of 16 time periods demonstrated that the change in TMS (ΔTMS) was better associated with tumor progression than the change in AFP (ΔAFP)[area under the curve (AUC) 0.800 and 0.783, respectively]. A composite score combining ΔTMS and ΔAFP further improved performance for detecting tumor progression with an AUC of 0.892.Conclusions:These findings indicate that ctDNA methylation scores can effectively evaluate changes in tumor burden without the need for tumor biopsy.