New Labyrinth Microfluidic Device Detects Circulating Tumor Cells Expressing Cancer Stem Cell Marker and Circulating Tumor Microemboli in Hepatocellular Carcinoma

• Published in: Scientific reports Vol. 9; no. 1; pp. 18575 - 11
• Main Authors: Wan, Shanshan, Kim, Tae Hyun, Smith, Kaylee J, Delaney, Ryan, Park, G-Su, Guo, Hui, Lin, Eric, Plegue, Thomas, Kuo, Ning, Steffes, John, Leu, Christopher, Simeone, Diane M, Razimulava, Nataliya, Parikh, Neehar D, Nagrath, Sunitha, Welling, Theodore H
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 09.12.2019; Nature Publishing Group UK
• Subjects: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Hepatocellular - blood; CD44 antigen; Cell survival; Disease Progression; Drug Resistance, Neoplasm; Embolism - metabolism; Hep G2 Cells; Hepatocellular carcinoma; Humans; Lab-On-A-Chip Devices; Liver cancer; Liver Neoplasms - blood; Metastases; Microfluidics; Microscopy, Fluorescence; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating - metabolism; Neoplastic Stem Cells - cytology; Peripheral blood; Stem cells; Translational Medical Research; Treatment Outcome; Tumor cells; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-54960-y

Hepatocellular Carcinoma (HCC) is one of the most lethal cancers with a high mortality and recurrence rate. Circulating tumor cell (CTC) detection offers various opportunities to advance early detection and monitoring of HCC tumors which is crucial for improving patient outcome. We developed and optimized a novel Labyrinth microfluidic device to efficiently isolate CTCs from peripheral blood of HCC patients. CTCs were identified in 88.1% of the HCC patients over different tumor stages. The CTC positivity rate was significantly higher in patients with more advanced HCC stages. In addition, 71.4% of the HCC patients demonstrated CTCs positive for cancer stem cell marker, CD44, suggesting that the major population of CTCs could possess stemness properties to facilitate tumor cell survival and dissemination. Furthermore, 55% of the patients had the presence of circulating tumor microemboli (CTM) which also correlated with advanced HCC stage, indicating the association of CTM with tumor progression. Our results show effective CTC capture from HCC patients, presenting a new method for future noninvasive screening and surveillance strategies. Importantly, the detection of CTCs with stemness markers and CTM provides unique insights into the biology of CTCs and their mechanisms influencing metastasis, recurrence and therapeutic resistance.