Circulating tumor cells as a prognostic and predictive marker in gastrointestinal stromal tumors: a prospective study

// Qiang Li 1, * , Xiaofei Zhi 1, * , Jianping Zhou 2, * , Ran Tao 1 , Jiaxuan Zhang 1 , Peisheng Chen 1 , Oluf Dimitri Roe 3, 4, 5 , Luning Sun 6 , Lilin Ma 1 1 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China 2 Department of Gastrointestinal Surgery, Affiliated Yixing Hospital of Jiangsu University, Yixing, China 3 Clinical Cancer Research Center, Aalborg University Hospital, Clinical Institute, Aalborg, Denmark 4 Cancer Clinic, Levanger Hospital, Nord-Trondelag Health Trust, Levanger, Norway 5 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway 6 Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Lilin Ma, e-mail: mall9052@163.com Keywords: circulating tumor cells, ANO1, DOG1, gastrointestinal stromal tumors, recurrence Received: October 16, 2015     Accepted: April 16, 2016     Published: May 2, 2016 ABSTRACT Background: Circulating tumor cells (CTC) are prognostic and predictive for several cancer types. Only limited data exist regarding prognostic or predictive impact of CTC on gastrointestinal stromal tumor (GIST) patients. The aim of our study was to elucidate the role of CTC in GIST patients. Results: A total of 121 GIST patients and 54 non-GIST samples were enrolled in the study. The cutoff value for ANO1 positive was 3*10 -5 and 65 (54%) GIST patients were defined as ANO1 positive. ANO1s were more frequently detected in unresectable patients. Tumor size, mitotic count and risk level were associated with ANO1 detection in resectable GIST patients. The presence of ANO1 significantly correlated with poor disease-free survival (15.3 versus 19.6 months, p = 0.038). Most patients turned ANO1-negative after surgery and inversely, all 21 patients with recurrence turned ANO1-positive with high ANO1 expression levels. Moreover, in the neoadjuvant setting, decline of ANO1 expression level correlated with the response of imatinib. Methods: Cells from peripheral blood mononuclear cells tested positive for anoctamin 1, calcium activated chloride channel, ANO1 (DOG1) were considered as tumor CTC of GISTs. The expression levels of ANO1 were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The highest level of ANO1 expression in non-GIST samples was used as the “cutoff” value. Conclusion: ANO1 detection by qRT-PCR in peripheral blood is of clinical potential for monitoring recurrence and evaluating therapeutic efficacy of imatinib for GIST patients.