Enumeration And Characterization Of Circulating Tumor Cells And Its Application In Advanced Gastric Cancer

Abstract

Boran Cheng,1,* Gangling Tong,1,* Xuan Wu,1,* Wenwu Cai,2,* Zhu Li,1,* Zhongyi Tong,2 Lirui He,1 Shaokang Yu,1 Shubin Wang1 1Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province 518036, People’s Republic of China; 2Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Boran Cheng; Shubin WangDepartment of Oncology, Peking University Shenzhen Hospital, No. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong Province 518036, People’s Republic of ChinaTel [phone]-5356Fax [phone]Email [email protected]; [email protected]: Advanced gastric cancer (aGC) has a high global incidence and a high mortality rate and because of its high malignancy and heterogeneity, the existing methods for prognosis are limited, and a new treatment model is necessary. Circulating tumor cells (CTCs) could be considered as a “liquid biopsy” for tumor diagnosis and for monitoring treatment responses and predicting clinical outcome. Clinical studies support the efficacy of programmed cell death 1 (PD-1) immunotherapy in a subset of aGC.Methods: Cell capture efficiency, as described by the CanPatrol CTC enrichment technique, was validated using artificial blood samples as well as blood samples from 32 aGC patients. Clinicopathologic data of patients were collected from the hospital information system. We used CanPatrol for CTC isolation, classification, and clinical analysis.Results: A cell capture efficiency of >80% was achieved. Significant correlation was observed between CTC enumeration and clinicopathology parameters, including the Lauren classification (r=0.470, P=0.008), perineural invasion (r=0.393, P=0.029), TNM stage (r=0.740, P<0.001), and Ki-67 level (r=0.510, P=0.005). When compared to the traditional methods, monitoring CTC subtypes exhibits higher sensitivity of evaluating the disease status. Enumeration of epithelial CTC subset and its relative abundance in the total CTC pool are highly correlated with clinical efficacy. CTC programmed cell death ligand-1 (PD-L1) could be successfully detected for immunotherapy in addition to PD-L1 immunohistochemistry and microsatellite instability.Conclusion: We provide a new method that allows for the simple and effective detection of CTCs in aGC. It has potential clinical applications in monitoring prognosis and guiding future individualized immunotherapy.Keywords: CTC enumeration, clinical response prediction, subgroup analysis, immune checkpoint therapy

Keywords

• CTCs enumeration
• clinical response prediction
• subgroup analysis
• immune checkpoint therapy.