关键词: Hepatocellular carcinoma Liquid biopsy Liver dysplastic nodules Metastatic nodules Radiofrequency ablation Recurrence prediction

来  源:   DOI:10.14218/JCTH.2023.00559   PDF(Pubmed)

Abstract:
UNASSIGNED: Hepatocellular carcinoma (HCC) cases with small nodules are commonly treated with radiofrequency ablation (RFA), but the recurrence rate remains high. This study aimed to establish a blood signature for identifying HCC with metastatic traits pre-RFA.
UNASSIGNED: Data from HCC patients treated between 2010 and 2017 were retrospectively collected. A blood signature for metastatic HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin, cell-free DNA (cfDNA) mutations, and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA performance. The HCC blood signature was validated in patients prospectively enrolled in 2021.
UNASSIGNED: Of 251 HCC patients in the retrospective study, 33.9% experienced recurrence within 1 year post-RFA. The HCC blood signature identified from these patients included des-γ-carboxy-prothrombin ≥40 mAU/mL with cfDNA mutation score, where cfDNA mutations occurred in the genes of TP53, CTNNB1, and TERT promoter. This signature effectively predicted 1-year post-RFA recurrence of HCC with 92% specificity and 91% sensitivity in the retrospective dataset, and with 87% specificity and 76% sensitivity in the prospective dataset (n=32 patients). Among 14 cases in the prospective study with biopsy tissues available, positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and microvasculature.
UNASSIGNED: This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease\'s early recurrence post-RFA.
摘要:
具有小结节的肝细胞癌(HCC)病例通常采用射频消融(RFA)治疗,但复发率仍然很高。这项研究旨在建立用于鉴定RFA前具有转移性特征的HCC的血液特征。
回顾性收集2010年至2017年间治疗的HCC患者的数据。根据甲胎蛋白和des-γ-羧基凝血酶原的血液水平建立了转移性HCC的血液特征,无细胞DNA(cfDNA)突变,以及在RFA执行前收集的冷冻储存血浆样品中靶基因的甲基化变化。在2021年前瞻性登记的患者中验证了HCC的血液特征。
在回顾性研究中的251例HCC患者中,33.9%在RFA后1年内复发。从这些患者中鉴定的HCC血液特征包括des-γ-羧基-凝血酶原≥40mAU/mL,cfDNA突变评分,其中cfDNA突变发生在TP53,CTNNB1和TERT启动子的基因中。该特征有效地预测了RFA后1年的HCC复发,在回顾性数据集中具有92%的特异性和91%的敏感性。在前瞻性数据集中,特异性为87%,敏感性为76%(n=32例)。在前瞻性研究中,有14例活检组织可用,HCC血液标记阳性与较高的HCC组织评分和较短的HCC细胞与微脉管系统之间的距离相关.
这项研究在RFA前的血液中建立了HCC血液特征,这可能反映了具有转移性特征的HCC,并且可能对预测RFA后疾病的早期复发很有价值。
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