Feasibility of a novel one-stop ISET device to capture CTCs and its clinical application

// Fangfang Chen 1, * , Shuyi Wang 1, * , Yuan Fang 1, * , Liang Zheng 1 , Xuan Zhi 2 , Boran Cheng 1 , Yuanyuan Chen 1 , Chunxiao Zhang 1 , Dongdong Shi 1 , Haibin Song 1 , Congli Cai 2 , Pengfei Zhou 2 , Bin Xiong 1 1 Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China 2 Department of Circulating Tumor Cells, YZY Medical Technological Company, Wuhan, China * These authors contributed equally to this work Correspondence to: Bin Xiong, email: binxiong1961@whu.edu.cn Keywords: circulating tumor cells (CTCs), clusters of circulating tumor cells (CTC-clusters), epithelial-mesenchymal transition (EMT), isolation method by size of epithelial tumor cells (ISET), colorectal cancer (CRC) Received: October 17, 2016      Accepted: November 24, 2016      Published: December 08, 2016 ABSTRACT Introduction: Circulating tumor cells (CTCs) play a crucial role in cancer metastasis. In this study, we introduced a novel isolation method by size of epithelial tumor cells (ISET) device with automatic isolation and staining procedure, named one-stop ISET ( os ISET) and validated its feasibility to capture CTCs from cancer patients. Moreover, we aim to investigate the correlation between clinicopathologic features and CTCs in colorectal cancer (CRC) in order to explore its clinical application. Results: The capture efficiency ranged from 80.3% to 88% with tumor cells spiked into medium while 67% to 78.3% with tumor cells spiked into healthy donors’ blood. In detection blood samples of 72 CRC patients, CTCs and clusters of circulating tumor cells (CTC-clusters) were detected with a positive rate of 52.8% (38/72) and 18.1% (13/72) respectively. Moreover, CTC positive rate was associated with factors of lymphatic or venous invasion, tumor depth, lymph node metastasis and TNM stage in CRC patients ( p < 0.01). Lymphocyte count and neutrophil to lymphocyte ratio (NLR) were significantly different between CTC positive and negative groups ( p < 0.01). Materials and Methods: The capture efficiency of the device was tested by spiking cancer cells (MCF-7, A549, SW480, Hela) into medium or blood samples of healthy donors. Blood samples of 72 CRC patients were detected by os ISET device. The clinicopathologic characteristics of 72 CRC patients were collected and the association with CTC positive rate or CTC count were analyzed. Conclusions: Our os ISET device was feasible to capture and identify CTCs and CTC-clusters from cancer patients. In addition, our device holds a potential for application in cancer management.