Circulating Tumor Cell‐Based mRNA Scoring System for Prognostication of Hepatocellular Carcinoma ‐ Translating HCC Tissue‐based mRNA Profiling into a Non‐invasive Setting

2021 ◽  
Author(s):  
Yi‐Te Lee ◽  
Na Sun ◽  
Minhyung Kim ◽  
Jasmine J. Wang ◽  
Benjamin V. Tran ◽  
...  
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.


Lab on a Chip ◽  
2019 ◽  
Vol 19 (15) ◽  
pp. 2549-2556 ◽  
Author(s):  
Xuejia Hu ◽  
Daoming Zhu ◽  
Ming Chen ◽  
Keke Chen ◽  
Hailiang Liu ◽  
...  

Precise and non-invasive circulating tumor cell isolation based on optical force using homologous erythrocyte binding in a microfluidic system.


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 ◽  
...  

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