术前血浆游离DNA染色体不稳定预测肝细胞癌微血管侵犯：一项前瞻性研究

Preoperative plasma cell-free DNA chromosomal instability predicts microvascular invasion in hepatocellular carcinoma: a prospective study.

作者信息

Shu Zheyue, Ye Ting, Wu Wei, Su Menghan, Wang Jingcheng, Zhang Min, Qian Ziliang, Huang Haifen, Zheng Shusen, Xia Qi

机构信息

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China.

NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China.

出版信息

BMC Cancer. 2025 May 13;25(1):867. doi: 10.1186/s12885-025-14268-9.

DOI:10.1186/s12885-025-14268-9

PMID:40361115

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12076900/

Abstract

BACKGROUND

Microvascular invasion (MVI) has been recognized as a risk factor for early recurrence after hepatectomy in patients with hepatocellular carcinoma (HCC). This study aimed to estimate the performance of an ultrasensitive chromosomal aneuploidy detector (UCAD) model for preoperative MVI prediction in operable HCC patients based on plasma cell-free DNA (cfDNA).

METHODS

A prospective study included HCC patients who underwent surgery in 2021. Preoperative peripheral plasma samples of eligible patients were collected to extract cfDNA, which was then subject to next generation sequencing. Low-coverage whole-genome sequencing data were analyzed for chromosomal instability using different parameters, including Z-score, chromosomal instability score (CIN score), tumor fraction (TFx) and a UCAD model (UCAD = CIN score + TFx + Z-score of all chromosomes). Receiver operating characteristic (ROC) curve was used to evaluate the performance of these parameters in preoperative MVI prediction.

RESULTS

Finally, a total of 74 patients with HCC who undergone hepatectomy were prospectively enrolled. Chromosomal instability was evaluated by copy number alterations and oncogenes MCL1 (located at 1q), MYC (located at 8q), TERT (located at 5p), EGFR (located at 7p), and VEGFA (located at 6p) were identified in plasma cfDNA. The UCAD model was a superior parameter in predicting preoperative MVI, with an area under curve (AUC) value 0.749 with a sensitivity of 0.938 specificity of 0.466. Univariate analysis revealed that tumor size (≥ 5 cm) and UCAD (> 0.199) significantly increased the risk of MVI, which were further demonstrated by multivariate analysis, with odd ratio of 1.338 (95%CI, 1.060-1.689) and 2.028 (95%CI, 1.053-3.908) (P < 0.05).

CONCLUSIONS

Our cfDNA-based UCAD model has shown a promising performance for preoperative MVI prediction in operable HCC patients.

TRIAL REGISTRATION

This study was registered at https://clinicaltrials.gov/ on 16 May 2022, retrospectively registered, Registration number: NCT05371873.

摘要

背景

微血管侵犯（MVI）已被公认为肝细胞癌（HCC）患者肝切除术后早期复发的危险因素。本研究旨在评估一种基于血浆游离DNA（cfDNA）的超灵敏染色体非整倍体检测（UCAD）模型对可手术切除的HCC患者术前MVI的预测效能。

方法

一项前瞻性研究纳入了2021年接受手术的HCC患者。收集符合条件患者的术前外周血样本以提取cfDNA，随后对其进行下一代测序。使用包括Z值、染色体不稳定评分（CIN评分）、肿瘤分数（TFx）和UCAD模型（UCAD = CIN评分 + TFx + 所有染色体的Z值）等不同参数，对低覆盖度全基因组测序数据进行染色体不稳定性分析。采用受试者工作特征（ROC）曲线评估这些参数在术前MVI预测中的效能。

结果

最终，共有74例接受肝切除术的HCC患者被前瞻性纳入研究。通过拷贝数改变评估染色体不稳定性，并在血浆cfDNA中鉴定出癌基因MCL1（位于1q）、MYC（位于8q）、TERT（位于5p）、EGFR（位于7p）和VEGFA（位于6p）。UCAD模型在预测术前MVI方面是一个优越的参数，曲线下面积（AUC）值为0.749，灵敏度为0.938，特异度为0.466。单因素分析显示肿瘤大小（≥5 cm）和UCAD（>0.199）显著增加了MVI的风险，多因素分析进一步证实了这一点，比值比分别为1.338（95%CI，1.060 - 1.689）和2.028（95%CI，1.053 - 3.908）（P < 0.05）。