Thaninee Prasoppokakorn1, Areeya Buntho1, Praewphan Ingrungruanglert2, Nipan Israsena2 3, Rungsun Rerknimitr1, Sombat Treeprasertsuk1 4, and Roongruedee Chaiteerakij1

1Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
2Excellence center for Stem Cell and Cell Therapy Research Unit, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
3Department of Pharmacology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
4Department of Biochemistry and Liver Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Background/Aims: CTCs, neoplastic cells released from primary tumor into blood circulation, are surrogate for tumor progression and metastasis. Detection of CTCs may facilitate treatment decision and monitoring treatment response and disease recurrence. We aimed to determine association between CTCs and HCC stages.

Methods: We collected 8-mL of peripheral blood from 73 HCC patients between April 2019 and August 2020 to identify CTCs, defined as cells positive for EpCAM and MUC1 on fluorescent microscopy.

Results: 56 (77%) were males (mean age: 60+12 years). There were 26 (36%), 22 (30%) and 25 (34%) patients with BCLC stage A, B, C, respectively. Overall CTCs detection rate was 79.5% (58/73). Patients with BCLC A, B, C had significantly different detection rates of 65.4% (17/26), 77.3% (17/22), and 96% (24/25), p=0.02, and tended to have different CTC numbers with mean CTCs of 2.5+3.5, 10.0+16.8 and 50.8+140.1 cells/8-mL, respectively, p=0.09. Patients with aggressive HCC had higher CTC number than those with less aggressive disease, in aspect of vascular invasion (44.4+138.6 vs. 9.3+25.3; p=0.22), lymph node metastasis (87.2+205.9 vs. 9.7+22.8; p=0.24), and distant metastasis (214.2+326.3 vs. 10.2+22.6; p=0.30). The AUROC of CTCs for predicting vascular invasion, lymph node metastasis, distant metastasis, and BCLC stage C were 0.72, 0.69, 0.80, and 0.75, respectively(Figure).

Conclusion: This pilot study demonstrates that advanced HCC patients have higher detection rate of peripheral CTCs positivity with tend to have more number of CTCs than those with early stage. Peripheral CTCs may be potential marker of HCC aggressiveness, which could guide staging and prognosis.

Keywords: Circulating Tumor Cells, Hepatocellular Carcinoma