CD133+CD54+CD44+ circulating tumor cells as a biomarker of treatment selection and liver metastasis in patients with colorectal cancer

// Chao Fang 1, 2, * , Chuanwen Fan 1, 2, * , Cun Wang 1 , Qiaorong Huang 3 , Wentong Meng 3 , Yongyang Yu 1 , Lie Yang 1 , Zhihai Peng 4 , Jiankun Hu 1 , Yuan Li 2 , Xianming Mo 3 , Zongguang Zhou 1, 2 1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China 2 Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 3 Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 4 Department of General Surgery, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Zongguang Zhou, email: zhou767@163.com Xianming Mo, email: xmingmo@scu.edu.cn Keywords: colorectal cancer, circulating tumor cells, CD133 + CD54 + CD44 + cellular subpopulation, liver metastasis, predictive biomarker Received: February 25, 2016     Accepted: September 20, 2016     Published: October 15, 2016 ABSTRACT Introduction : Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM). Results: The expression of CD133 + and CD133 + CD54 + CD44 + cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis ( P <0.001). Multivariate analysis proved the association between the expression of CD133 + CD44 + CD54 + cellular subpopulation and the existence of CRC-LM ( P <0.001). The combination of abdominal CT/MRI, CEA and the CD133 + CD44 + CD54 + cellular subpopulation showed increased detection and discrimination rate for liver metastasis, with a sensitivity of 88.2% and a specificity of 92.4%. Meanwhile, it also show accurate predictive value for liver metastasis (OR=2.898, 95% C.I.1.374–6.110). Materials and Method: Flow cytometry and multivariate analysis was performed to detect the expression of cancer initiating cells the correlation between cellular subpopulations and liver metastasis in patients with CRC. The receiver operating characteristic curves combined with the area under the curve were generated to compare the predictive ability of the cellular subpopulation for liver metastasis with current CT and MRI images. Conclusions: The identification, expression and application of CTC subpopulations will provide an ideal cellular predictive marker for CRC liver metastasis and a potential marker for further investigation.