AUTHOR=Chen Jing , Luo Yuhong , Xi Xiaoxue , Li Haixia , Li Shufen , Zheng Lei , Yang Dinghua , Cai Zhen 

TITLE=Circulating tumor cell associated white blood cell cluster as a biomarker for metastasis and recurrence in hepatocellular carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.931140

DOI=10.3389/fonc.2022.931140

ISSN=2234-943X

ABSTRACT=Background: Recently in vivo study demonstrated that circulating tumor cell associated white blood cell (CTC-WBC) cluster possesses much greater potential than single CTC. We aim to explore the correlation between CTC-WBC cluster and the clinicopathological characteristics of hepatocellular carcinoma (HCC) patients to seek novel biomarkers for HCC metastasis and recurrence.
Methods: We retrospectively analyzed 136 HCC patients from October 2014 to March 2020 received CTCs test using CanPatrol CTC enrichment technique. The correlation between the clinical features and total CTCs, EMT-CTCs and CTC-WBC cluster were analyzed by chi-square test. The ROC curves were simulated for evaluating the diagnostic performance of CTCs parameters in HCC metastasis. Patients were followed up from February 2015 to November 2021 and the relapse-free survival (RFS) was analyzed using the Kaplan-Meier curve.
Results: Totally 93.4% (127/136) and 31.6% (43/136) of HCC patients had detectable CTCs and CTC-WBC cluster. Baseline CTC-WBC cluster was closely correlated with microvascular invasion, portal vein tumor thrombus, and extrahepatic metastasis in pre-treatment HCC patients (P < 0.05). The simulated ROC curves presented an AUC of 0.821 for CTC-WBC cluster (sensitivity 90.0% and specificity 93.7%) in discriminating metastasis from non-metastatic HCC, which was higher than that for total CTCs (0.718) and EMT-CTCs (0.716). Further follow-up analysis showed that compared to the CTC-WBC cluster negative group (< 1/5 mL), patients in the CTC-WBC cluster positive group (≥ 1/5 mL) presented increased relapse ratio (60.0% versus 17.9%) and shorter RFS (22.9 versus 53.8 months). Dynamic analysis of CTCs parameters showed that total CTCs level, EMT-CTCs proportion and CTC-WBC cluster were decreased after microwave ablation treatment, while CTC-WBC cluster increased average 10 months in advance of imaging (MRI) diagnosed recurrence.
Conclusion: CTC-WBC cluster is a promising biomarker for the metastasis diagnosis and prognosis of HCC metastasis. Dynamic monitoring of CTC-WBC cluster is an effective method for early detection and intervention of HCC recurrence and metastasis.