4 research outputs found

    Correlation Between Circulating Tumor Cell DNA Genomic Alterations and Mesenchymal CTCs or CTC-Associated White Blood Cell Clusters in Hepatocellular Carcinoma

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    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

    Beyond epithelial circulating tumour cells (CTCs) : establishing important methods for CTC isolation and analysis

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    This thesis has demonstrated the various applications for antibody-based CTC capture, extending beyond conventional methods. We reported the inclusion of EMT-markers for detection and characterisation of EMT-CTCs in the ovarian cancer setting. This methodological advancement may prove a critical step in understanding the role EMT plays in CTC formation, metastasis and potentially therapeutic resistance. In addition, we explored integration of electron microscopy methods into CTC sample processing, allowing for ultrastructure analysis of CTCs and improving the tools to help understand CTC biology. Finally, we explored antibody-based CTC isolation methods in the melanoma setting with additional biomarker PD-L1 detection, enabling real-time monitoring of therapy response to PD-1 inhibitors. Overall, the knowledge gained from this thesis will aid the CTC research field from three different perspectives: (1) The clinical perspective: capitalize on CTC detection by adding important biomarker detection that may indicate response to therapy; (2) The technical perspective: demonstrating feasibility of integrating electron microscopy sample preparation into CTC analyses; (3) The biological perspective: establishing EMT detection in a range of cancers