Research Papers:

Expression and clinical relevance of epithelial and mesenchymal markers in circulating tumor cells from colorectal cancer

Ren Zhao, Zhen Cai, Sheng Li, Yong Cheng, Hua Gao, Fang Liu, Shiyang Wu, Suyan Liu, Yan Dong, Lei Zheng, Wenbin Zhang, Xiaojun Wu and Xueqing Yao _

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Oncotarget. 2017; 8:9293-9302. https://doi.org/10.18632/oncotarget.14065

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Ren Zhao1,*, Zhen Cai2,*, Sheng Li3,*, Yong Cheng4, Hua Gao5, Fang Liu6, Shiyang Wu6, Suyan Liu6, Yan Dong6, Lei Zheng2, Wenbin Zhang7, Xiaojun Wu8, Xueqing Yao3

1Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

2Department of Laboratory Medicine, Sino-UK Circulating Biomarkers’ Exploration and Detection Center, Nanfang Hospital, Southern Medical University, Guangzhou, China

33Department of General surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China

4Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China

5Department of General Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

6SurExam Bio-Tech Co., Guangzhou, China

7Department of Gastrointestinal Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

8Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

*These authors are contributed equally to this work

Correspondence to:

Xiaojun Wu, email: [email protected]

Xueqing Yao, email: [email protected]

Keywords: colorectal cancer, circulating tumor cells, epithelial-mesenchymal transition, clinical stage, metastasis

Received: September 27, 2016     Accepted: December 13, 2016     Published: December 21, 2016


Circulating tumor cells (CTCs) with phenotypic hallmarks of epithelial-mesenchymal transition (EMT) reportedly contribute to tumor metastasis in different cancer types. We therefore evaluated the expression of EMT markers in CTCs obtained from a large cohort of Chinese patients with colorectal cancer (CRC) and investigated their clinical relevance. The CanPatrolTM CTC enrichment technique was used to isolate and classify CTCs. CTCs were detected in 1046 of 1203 patients (86.9%), and three phenotypes were identified based on the expression of epithelial and mesenchymal markers: epithelial CTCs, biophenotypic (epithelial/mesenchymal) CTCs, and mesenchymal CTCs. Total CTC numbers positively correlated with both clinical stage and lymph node metastasis and distant metastasis. Furthermore, both biophenotypic and mesenchymal, but not epithelial, CTCs, correlated with the above parameters, suggesting CTCs displaying a mesenchymal phenotype denote more aggressive disease and metastatic potential. This is the first study to demonstrate a significant correlation between CTCs displaying a mesenchymal phenotype and both clinical stage and metastasis in a large cohort of patients with CRC. Our findings suggest that assessment of not only epithelial, but also mesenchymal markers in CTC analyses may offer valuable assistance for tumor staging and metastasis evaluation in patients with CRC.

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