scholarly journals Circulating Tumor-Cell-Associated White Blood Cell Clusters in Peripheral Blood Indicate Poor Prognosis in Patients With Hepatocellular Carcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Qiong Luo ◽  
Chunming Wang ◽  
Bangjian Peng ◽  
Xiaoyu Pu ◽  
Lei Cai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Blood Cell ◽  
Tumor Cell ◽  
White Blood Cell ◽  
Peripheral Blood ◽  
Poor Prognosis ◽  
Circulating Tumor Cell ◽  
Cell Clusters

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunming Wang ◽  
Qiong Luo ◽  
Wenbin Huang ◽  
Cheng Zhang ◽  
Hangyu Liao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Blood Cell ◽  
Tumor Cell ◽  
Clinical Application ◽  
White Blood Cell ◽  
Peripheral Blood ◽  
Hot Spot ◽  
Circulating Tumor Cell ◽  
Genomic Alterations ◽  
Genomic Changes

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.

scholarly journals Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers

2017 ◽  
Vol 77 (18) ◽  
pp. 5194-5206 ◽  
Author(s):  
Vasudha Murlidhar ◽  
Rishindra M. Reddy ◽  
Shamileh Fouladdel ◽  
Lili Zhao ◽  
Martin K. Ishikawa ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Poor Prognosis ◽  
Early Stage ◽  
Circulating Tumor Cell ◽  
Lung Cancers ◽  
Cell Clusters

Detection of circulating tumor cell clusters in the peripheral blood of colorectal cancer patients

2000 ◽  
Vol 118 (4) ◽  
pp. A278
Author(s):  
Andras Ladanyi ◽  
Bela Molnar ◽  
Lenke M. Tanko ◽  
Lidia Sreter ◽  
Zsolt Tulassay
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Circulating Tumor Cell ◽  
Cell Clusters ◽  
Colorectal Cancer Patients

scholarly journals Epithelial-Mesenchymal-Transition-Like Circulating Tumor Cell-Associated White Blood Cell Clusters as a Prognostic Biomarker in HR-Positive/HER2-Negative Metastatic Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiuwen Guan ◽  
Chunxiao Li ◽  
Yiqun Li ◽  
Jiani Wang ◽  
Zongbi Yi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Blood Cell ◽  
White Blood Cell ◽  
Peripheral Blood ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Blood Samples ◽  
Mesenchymal Transition ◽  
Cell Clusters

BackgroundAlthough positive Circulating tumor cells (CTCs) status has been validated as a prognostic marker in breast cancer, the interaction between immune cells and CTCs during the progress of Epithelial-mesenchymal-transition (EMT), and the clinical implications of CTC-associated white blood cell clusters (CTC-WBC clusters) for metastatic breast cancer are largely uncharacterized.MethodsWe optimized a filter-based method combined with an RNA in situ hybridization technique according to the epithelial- and mesenchymal-markers to analyze EMT in CTC-WBC clusters. Serial peripheral blood samples from 135 patients with Hormone receptor (HR)-positive/HER2-negative metastatic breast cancer receiving first-line chemotherapy with docetaxel plus capecitabine were prospectively collected until disease progression from Nov 2013 to March 2019. Follow-up data collection was conducted until July 2020.ResultsA total of 452 blood samples at all time-points were collected and analyzed. Median age of the cohort was 51.0 years (range, 27 to 73 years), and most of them (76.3%) had visceral metastases. Median progression-free survival (PFS) was 10.6 months (95% CI, 8.8 to 12.3 months). The presence of EMT-like CTC-WBC clusters was more frequently evident among patients with simultaneous bone and lymph node metastases (87.5% vs 36.2%, P=0.006), whereas no associations were observed between CTC-WBC clusters and other clinicopathologic characteristics before chemotherapy. The patients with EMT-like CTC-WBC clusters tended to show a significantly increased number of total CTC count (median,19.0 vs 5.0, P<0.001). The patients with at least one detectable EMT-like CTC-WBC cluster at baseline were characterized by significantly worse PFS, when compared to the patients with no EMT-like CTC-WBC clusters detected (7.0 vs 10.7 months, P=0.023), and those with five or more epithelial-based CTCs detected per 5mL of peripheral blood (7.0 vs 12.7 months, P=0.014). However, the total CTC-WBC clusters were not correlated with patients’ survival in the cohort (8.4 vs 10.6 months, P=0.561).ConclusionsOur data provide evidence that the emergence of CTC-WBC clusters underwent EMT before treatment is associated with significantly poorer PFS in HR-positive/HER2-negative metastatic breast cancer patients receiving docetaxel plus capecitabine, which may be used as a parameter to predict the clinical outcomes and a potential target for individualized therapy.

Ex vivo propagation and characterization of circulating tumor cell clusters from late stage prostate cancer patients.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 314-314 ◽  
Author(s):  
James Lim ◽  
Charles J. Ryan ◽  
Bruce Adams ◽  
Jeff Hough ◽  
Tianna Chow
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Biomarker Discovery ◽  
Ex Vivo ◽  
Circulating Tumor Cell ◽  
Cell Clusters

314 Background: Cells shed by a tumor into the bloodstream upon metastasis present an opportunity to study the properties of these cells for biomarker discovery, drug development, and personalized therapy. Enrichment and expansion of circulating tumor cells (CTCs) in culture enables molecular characterization not readily available for rare cells. Here, we demonstrate the successful identification and culture of rare circulating tumor cell clusters from peripheral blood of metastatic castration resistant prostate cancer patients (mCRPC). Methods: The approach to isolate CTC clusters relies on nucleated cell enrichment via Ficoll-based centrifugation from 15 mL of peripheral blood. A collagen-based cell-binding substrate was used to capture cell clusters with preferential affinity for collagen (i.e. epithelial-like cells). Hypoxic and pressurized culturing conditions were used to maintain and propagate adhered CTC clusters. After 7 days in culture, immunofluorescence imaging, qPCR and/or mRNAseq were performed on CTC clusters that had formed colonies. Results: Blood samples processed within 3 hours from time of draw yielded a 25% success rate (4/16) for identifying PSMA+/EpCAM+/CD45- CTC colonies. Morphologically distinct CTC colonies cultivated at 1% oxygen and increased hydrostatic pressure (2 PSI) were positive for PSMA and EpCAM staining as observed via confocal microscopy, with individual colonies ranging from approximately 50 to 1000 in cell number. Colonies consistently revealed white blood cell contaminants (T-cells and dendritic cells, 10 to 30% of colony) that did not appear to perturb colony growth. CTC colonies were collected for qPCR analysis and mRNAseq via laser-capture microdissection and/or micropipetting. Genomic analysis revealed differential gene expression patterns between CTC colonies cultured from the same patient sample, with a subset expressing neuroendocrine like signatures (AURKA), stem cell markers (SOX2, OCT4), and immuno-oncology relevant markers (PD-L1, CTLA4). Conclusions: In conclusion, we show that viable CTCs are amenable to ex vivo culture, providing both functional and molecular insights into a sub-population of CTCs with propagating potential. The presence of T-cells and dendritic cells on CTC colonies warrants further investigation, and may provide unique insights into immune-tumor interactions. The culturing platform is currently being evaluated as a research tool for biomarker discovery and as a clinical tool for disease monitoring and treatment decision-making.

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