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

作者：Claudia Campani, Sandrine Imbeaud, Gabrielle Couchy, Marianne Ziol, Théo Z. Hirsch, Sandra Rebouissou, Bénédicte Noblet, Pierre Nahon, Katia Hormigos, Sabrina Sidali, Olivier Séror, Valérie Taly, Nathalie Ganne‐Carrié, Pierre Laurent‐Puig, Jessica Zucman‐Rossi, Jean‐Charles Nault · 发表于：Gut · 年份：2024 · DOI：10.1136/gutjnl-2024-331956 · 被引用次数：51 · 研究领域：Cancer Genomics and Diagnostics、Pancreatic and Hepatic Oncology Research、Lung Cancer Treatments and Mutations

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 ...