ArticleFrontiers in oncology2021
The Presence of Circulating Tumor Cell Cluster Characterizes an Aggressive Hepatocellular Carcinoma Subtype.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- PD-L1 status on circulating tumor cells: a promising predictor in advanced lung cancer with PD-1/PD-L1 immunotherapies.European journal of medical research · 2026Article
- PD-L1 expression on circulating tumor cells for predicting clinical outcomes in patients with hepatocellular carcinoma receiving PD-(L)1 blockade and targeted therapy.Journal for immunotherapy of cancer · 2026Article
- Unfolded protein response kinase PERK supports survival and metastasis of circulating tumor cell clusters via SAM synthesis and H3K4me3-dependent PDGFB signaling.Cancer communications (London, England) · 2025Article
- Exploring Circulating Tumor Cells: Detection Methods and Biomarkers for Clinical Evaluation in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2024Review
- A Preliminary Analysis of Circulating Tumor Microemboli from Breast Cancer Patients during Follow-Up Visits.Current oncology (Toronto, Ont.) · 2024Article
- Research progress on the multi-omics and survival status of circulating tumor cells.Clinical and experimental medicine · 2024Review
- EpCAM-positive circulating tumor cells and serum AFP levels predict outcome after curative resection of hepatocellular carcinoma.Scientific reports · 2023Article
- Prognostic value of preoperative circulating tumor cells for hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score analysis.Journal of cancer research and clinical oncology · 2023Article
- A model for the dissemination of circulating tumour cell clusters involving platelet recruitment and a plastic switch between cooperative and individual behaviours.BMC ecology and evolution · 2023Article
- Tumor-derived proliferative CTCs and CTC clusters predict aggressiveness and early recurrence in hepatocellular carcinoma patients.Cancer medicine · 2023Article
- Circulating tumor cells as a prognostic biomarker in patients with hepatocellular carcinoma.Scientific reports · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGrowing evidence suggests that circulating tumor cell (CTC) clusters may be an important factor in the metastatic process, but their role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to characterize the molecular and clinical features of CTC cluster-positive human HCC and to assess its prognostic value in HCC patients.
methodsThe CTCs and CTC clusters were evaluated in 204 HCC patients using CellSearch™ System. The counts of CTCs and CTC clusters were correlated with different clinical features, while their associations with progression-free survival (PFS) and overall survival (OS) were evaluated integrally and hierarchically by Kaplan-Meier estimates or Cox proportional regression analysis. Five cases each of CTC cluster-negative and cluster-positive patients were selected for RNA-sequencing analysis. The results of gene enrichment analysis were further verified using tissue microarray (TMA) by immunohistochemistry (IHC).
resultsCTCs and CTC clusters were detected in 76 (37.3%) and 19 (9.3%) of 204 preoperative samples, respectively. CTC cluster-positive HCC represented an aggressive HCC phenotype with larger tumor size, more frequent microvascular invasion, and higher tumor stages. The survival of HCC patients utilizing CTCs and CTC clusters individually showed prognostic significance, while joint analysis revealed patients in Group III (CTC ≥ 2 and CTC cluster > 0) had the worst outcome. Stratified analysis of outcomes in Barcelona Clinic Liver Cancer (BCLC) and tumor-node-metastasis (TNM) stages indicated that patients with CTC clusters had significantly poorer prognosis in each stage than those without CTC clusters. Moreover, the RNA sequencing and TMA staining results showed that CTC cluster-positive HCCs were usually associated with Wnt/β-catenin signaling activation.
conclusionThe presence of CTC clusters characterizes an aggressive HCC subtype. CTC clusters may be used as a biomarker in predicting the prognosis on each stage of malignancy in HCC, which provides evidence for formulating therapeutic strategies for more precise treatment.
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