Abstract 4823: Circulating tumor cell miR-27a overexpression as a novel mechanism of hepatocellular carcinoma metastasis

Author(s):  
Olorunseun O. Ogunwobi ◽  
Chen Liu
2021 ◽  
Vol 11 ◽  
Author(s):  
Jing-Jing Yu ◽  
Chang Shu ◽  
Hui-Yuan Yang ◽  
Zhao Huang ◽  
Ya-Ni Li ◽  
...  

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.


2013 ◽  
Vol 6 (4) ◽  
pp. 420-428 ◽  
Author(s):  
Ivonne Nel ◽  
Hideo A. Baba ◽  
Judith Ertle ◽  
Frank Weber ◽  
Barbara Sitek ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunming Wang ◽  
Qiong Luo ◽  
Wenbin Huang ◽  
Cheng Zhang ◽  
Hangyu Liao ◽  
...  

PurposeLiquid biopsy is attracting attention as a method of real-time monitoring of patients with tumors. It can be used to understand the temporal and spatial heterogeneity of tumors and has good clinical application prospects. We explored a new type of circulating tumor cell (CTC) enrichment technology combined with next-generation sequencing (NGS) to analyze the correlation between genomic alterations in circulating tumor cells of hepatocellular carcinoma and the counts of mesenchymal CTCs and CTC-associated white blood cell (CTC-WBC) clusters.MethodsWe collected peripheral blood samples from 29 patients with hepatocellular carcinoma from January 2016 to December 2019. We then used the CanPatrol™ system to capture and analyze mesenchymal CTCs and CTC-WBC clusters for all the patients. A customized Illumina panel was used for DNA sequencing and the Mann–Whitney U test was used to test the correlation between mesenchymal CTCs, CTC-WBC cluster counts, and specific genomic changes.ResultsAt least one somatic hotspot mutation was detected in each of the 29 sequenced patients. A total of 42 somatic hot spot mutations were detected in tumor tissue DNA, and 39 mutations were detected in CTC-DNA, all of which included common changes in PTEN, MET, EGFR, RET, and FGFR3. The number of mesenchymal CTCs was positively correlated with the somatic genomic alterations in the PTEN and MET genes (PTEN, P = 0.021; MET, P  = 0.008, Mann–Whitney U test) and negatively correlated with the somatic genomic alterations in the EGFR gene (P = 0.006, Mann–Whitney U test). The number of CTC-WBC clusters was positively correlated with the somatic genomic alterations in RET genes (P  = 0.01, Mann–Whitney U test) and negatively correlated with the somatic genomic alterations in FGFR3 (P = 0.039, Mann–Whitney U test).ConclusionsWe report a novel method of a CTC enrichment platform combined with NGS technology to analyze genetic variation, which further demonstrates the potential clinical application of this method for spatiotemporal heterogeneity monitoring of hepatocellular carcinoma. We found that the number of peripheral blood mesenchymal CTCs and CTC-WBC clusters in patients with hepatocellular carcinoma was related to a specific genome profile.


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e22033-e22033
Author(s):  
Holly Rochefort ◽  
Anthony B. El-Khoueiry ◽  
Christina Ann To ◽  
Yucheng Xu ◽  
Tong Xu ◽  
...  

2021 ◽  
Author(s):  
Zhitao Chen ◽  
tielong Wang ◽  
Chuanbao Chen ◽  
Xitao Hong ◽  
Jia Yu ◽  
...  

Abstract Introduction: It is of great significance to confirm reliable indicators for the guidance of pretransplant radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). In this study, we aim to investigate whether circulating tumor cell (CTC) status is clinical indicator for RFA before liver transplantation (LT) in HCC patients. Method: 79 HCC patients with pretransplant CTC analysis were enrolled in this retrospective study. Clinical outcomes including recurrence and survival were compared and analyzed between patients with and without pretransplant RFA. Result Forty-two patients were detected as CTC- positive and 18 patients received pretransplant RFA. Recurrence was correlated with CTC count (P = 0.024), tumor number (P = 0.035), liver cirrhosis (P = 0.001), Milan criteria (P = 0.003) and University of California San Francisco (UCSF) criteria (P = 0.001). Kaplan-Meier analysis revealed that patients with CTC-positive had higher recurrence rate (P = 0.0257). For CTC-positive patients, the recurrence rate of pretransplant RFA group were significantly lower than non- pretransplant RFA group (0 vs. 46.7%, P = 0.0236). For CTC-negative patients, both recurrence rate and OS rate were similar and without significantly differences. In multivariate analysis, pretransplant RFA was the independent factor for recurrence (P = 0.025). Conclusion Pretransplant CTC status can guide the administration of pretransplant RFA in HCC patients which can reduce recurrence in CTC-positive HCC patients.


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