Circulating Tumor Cells as a Biomarker to Assist Molecular Diagnosis for Early Stage Non-Small Cell Lung Cancer

• Main Authors: He Y, Shi J, Schmidt B, Liu Q, Shi G, Xu X, Liu C, Gao Z, Guo T, Shan B
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-02-01
• Series: Cancer Management and Research
• Subjects: cellcollector; in vivo detection; pd-l1; gene mutation; next generation sequencing
• Online Access: https://www.dovepress.com/circulating-tumor-cells-as-a-biomarker-to-assist-molecular-diagnosis-f-peer-reviewed-article-CMAR

Yutong He,1 Jin Shi,1 Bernd Schmidt,2 Qingyi Liu,3 Gaofeng Shi,4 Xiaoli Xu,5 Congmin Liu,1 Zhaoyu Gao,1 Tiantian Guo,1 Baoen Shan1 1Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of China; 2Department of Internal Medicine - Pneumology and Sleep Medicine, Central Emergency Room, Palliative Medicine, DRK Kliniken Berlin, Berlin 13359, Germany; 3Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of China; 4Department of Radiology, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of China; 5Follow-Up Centre, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of ChinaCorrespondence: Baoen ShanCancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, People’s Republic of ChinaTel/Fax [phone]Email [e-mail] and Objective: Compared with tissue biopsy, liquid biopsy is the most preferable non-invasive promising method in personalized medicine, although it has many limitations in isolating circulating tumor cells (CTC). Lung cancer associated mortality is drastically increased due to a shortfall of early-stage detection, which remains a challenge. Herein, we aimed to detect lung cancer at an early-stage using CellCollector device.Methods: 39,627 volunteers underwent low-dose computed tomography; 2508 cases with pulmonary nodules and 7080 with no pulmonary nodules were chosen. After follow-up, 24 patients were diagnosed with early-stage non-small cell lung cancer (NSCLC), and subjected to CTC detection using CellCollector, along with 72 healthy volunteers. Immunofluorescence staining for EpCAM/CKs and CD45 were performed for CTC validation.Results: Fifteen out of twenty-four (stage I, n = 18; stage II, n = 6) early-stage lung cancer patients were found to be CTC-positive, whereas no CTC was found in the control group. Genetic mutation of TP53, ERBB2, PDGFRA, CFS1R and FGFR1 in the CTC revealed 71.6% of the mutation sites similar to the tumor tissues of 13 patients. Molecular characterization revealed higher expression of protein PD-LI in CTC (40%) as compared to tumor tissue (26.7%). Moreover, CTC clusters were detected in 40% of patients.Conclusion: CTC detection using the CellCollector in early-stage NSCLC had a relative high capture rate. Moreover, CTC analysis is a prospective setting for molecular diagnostic in cases when tumor tissue biopsy is not desirable.Keywords: CellCollector, in vivo detection, PD-L1, gene mutation, next generation sequencing