Integrated analysis of circulating tumour cells and circulating tumour DNA to detect minimal residual disease in hepatocellular carcinoma

作者：Lina Zhao, Liping Jiang, Yunhe Liu, Xuebing Wang, Jinge Song, Yulin Sun, Yinlei Bai, Xiu Rong Dong, Li‐Ying Sun, Jianxiong Wu, Yuchen Jiao, Xiaohang Zhao · 发表于：Clinical and Translational Medicine · 年份：2022 · DOI：10.1002/ctm2.793 · 被引用次数：20 · 研究领域：Cancer Genomics and Diagnostics、Cancer Cells and Metastasis、Hepatocellular Carcinoma Treatment and Prognosis

Dear Editor, Recurrence is the major reason for mortality after hepatectomy or liver transplantation surgery for hepatocellular carcinoma (HCC).1-4 It is difficult to precisely manage adjuvant therapy to prevent recurrence after surgery. Here, we demonstrated that an integrated strategy of monitoring circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) could accurately detect minimal residual disease (MRD) and precisely predict recurrence in patients with HCC.5-7 A total of 80 patients with HCC were enrolled in this study, and 66 were eligible for analysis using postoperative serial blood samples (Figure 1A, Figure S1; Table S1). CTCs were positively selected by the asialoglycoprotein receptor using a microfluidic system and identified with pancytokeratins (Figure 1B). The first postoperative blood samples were analyzed for recurrence risk evaluation. Postoperative CTC positivity was significantly correlated with worse recurrence-free survival (RFS) rates, with a sensitivity of 75% and specificity of 86.8% (p < .0001; hazard ratio [HR] 8.40, 95% confidence interval [CI] = 3.52–20.05) (Figure 2A, Table S2). To assess the ctDNA fraction, we first tested an approach using a personalized panel targeting mutations from whole-exome sequencing (PPWES). Briefly, we performed WES on the tumour samples and selected ∼15 somatic mutations for each case (Tables S4, S5). A personalized assay was designed to profile the mutations in the matched ctDNA sample with mutation-capsu...