Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments.

IF 23 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Pub Date : 2024-10-07 DOI:10.1136/gutjnl-2024-331956

Claudia Campani, Sandrine Imbeaud, Gabrielle Couchy, Marianne Ziol, Theo Z Hirsch, Sandra Rebouissou, Bénédicte Noblet, Pierre Nahon, Katia Hormigos, Sabrina Sidali, Olivier Seror, Valerie Taly, Nathalie Ganne Carrie, Pierre Laurent-Puig, Jessica Zucman-Rossi, Jean-Charles Nault

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引用次数: 0

Abstract

Objective: Circulating tumour DNA (ctDNA) is a promising non-invasive biomarker in cancer. We aim to assess the dynamic of ctDNA in patients with hepatocellular carcinoma (HCC).

Design: We analysed 772 plasmas from 173 patients with HCC collected at the time of diagnosis or treatment (n=502), 24 hours after locoregional treatment (n=154) and during follow-up (n=116). For controls, 56 plasmas from patients with chronic liver disease without HCC were analysed. All samples were analysed for cell free DNA (cfDNA) concentration, and for mutations in TERT promoter, CTNNB1, TP53, PIK3CA and NFE2L2 by sequencing and droplet-based digital PCR. Results were compared with 232 corresponding tumour samples.

Results: In patients with active HCC, 40.2% of the ctDNA was mutated vs 14.6% in patients with inactive HCC and 1.8% in controls (p<0.001). In active HCC, we identified 27.5% of mutations in TERT promoter, 21.3% in TP53, 13.1% in CTNNB1, 0.4% in PIK3CA and 0.2% in NFE2L2, most of the times similar to those identified in the corresponding tumour. CtDNA mutation rate increased with advanced tumour stages (p<0.001). In 103 patients treated by percutaneous ablation, the presence and number of mutations in the ctDNA before treatment were associated with higher risk of death (p=0.001) and recurrence (p<0.001). Interestingly, cfDNA concentration and detectable mutations increased 24 hours after a locoregional treatment. Among 356 plasmas collected in 53 patients treated by systemic treatments, we detected mutations at baseline in 60.4% of the cases. In patients treated by atezolizumab-bevacizumab, persistence of mutation in ctDNA was associated with radiological progression (63.6% vs 36.4% for disappearance, p=0.019). In two patients progressing under systemic treatments, we detected the occurrence of mutations in CTNNB1 in the plasma that was subclonal in the tumour for one patient and not detectable in the tumour for the other one.

Conclusion: ctDNA offers dynamic information reflecting tumour biology. It represents a non-invasive tool useful to guide HCC clinical management.

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不同肿瘤分期和治疗方法的肝细胞癌患者体内的循环肿瘤 DNA。

目的：循环肿瘤DNA（ctDNA）是一种很有前景的非侵入性癌症生物标志物。我们旨在评估肝细胞癌（HCC）患者体内ctDNA的动态变化：我们分析了173名HCC患者在诊断或治疗时（502人）、局部治疗后24小时（154人）和随访期间（116人）采集的772个血浆。在对照组中，分析了 56 例未患 HCC 的慢性肝病患者的血浆。对所有样本进行了细胞游离 DNA（cfDNA）浓度分析，并通过测序和液滴式数字 PCR 分析了 TERT 启动子、CTNNB1、TP53、PIK3CA 和 NFE2L2 的突变情况。结果与232份相应的肿瘤样本进行了比较：在活动性HCC患者中，40.2%的ctDNA发生突变，而在非活动性HCC患者中，突变率为14.6%，对照组为1.8%（pTERT启动子、TP53、CTNNB1、PIK3CA和NFE2L2的突变率分别为21.3%、13.1%、0.4%和0.2%，大部分时间与相应肿瘤中发现的突变率相似）。CtDNA突变率随肿瘤晚期而增加（一名患者血浆中的pCTNNB1在肿瘤中为亚克隆，而另一名患者在肿瘤中检测不到。结论：ctDNA 可提供反映肿瘤生物学特性的动态信息，是指导 HCC 临床治疗的一种非侵入性工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gut 医学-胃肠肝病学

CiteScore

45.70

自引率

2.40%

发文量

284

审稿时长

1.5 months

期刊介绍： Gut is a renowned international journal specializing in gastroenterology and hepatology, known for its high-quality clinical research covering the alimentary tract, liver, biliary tree, and pancreas. It offers authoritative and current coverage across all aspects of gastroenterology and hepatology, featuring articles on emerging disease mechanisms and innovative diagnostic and therapeutic approaches authored by leading experts. As the flagship journal of BMJ's gastroenterology portfolio, Gut is accompanied by two companion journals: Frontline Gastroenterology, focusing on education and practice-oriented papers, and BMJ Open Gastroenterology for open access original research.