机构：[1]Department of Immunology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China[2]State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China[3]BGI-Shenzhen, Shenzhen 518083, China[4]Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China[5]Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, China四川大学华西医院[6]Department of Pulmonary Oncology, Affiliated Hospital, Academy of Military Medical Science, Beijing 100071, China[7]Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China[8]Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing 100853, China[9]Molecular Disease Biology Section, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Danish Cancer Society, DK-2100 Copenhagen, Denmark[10]Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense C, Denmark[11]The Guangdong Enterprise Key Laboratory of Human Disease Genomics, BGI-Shenzhen, Shenzhen 518083, China[12]Shenzhen Key Laboratory of Transomics Biotechnologies, BGI-Shenzhen, 518083 Shenzhen, China[13]James D. Watson Institute of Genome Science, 310008 Hangzhou, China[14]Department of Oncology, Odense University Hospital, DK-5000 Odense C, Denmark[15]Hubei Provincial Cooperative, Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 30068, China[16]Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 10021, China[17]Institute of Environmental Health and Related Product Safety, China CDC, Beijing 10021, China[18]Laborartory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China[19]Lung Cancer Center, Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, China四川大学华西医院
Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326 blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Moreover, monitoring CTC values provided an efficient treatment response indicator in hematological malignancies. Compared to CellSearch, our method detected significantly higher positive rates in 40 NSCLC in all stages, including N0M0, N+M0 and M1, and was less affected by chemotherapy. This simple, robust and clinically-applicable technology detects viable CTCs from solid and hematopoietic malignancies in early to late stages, and significantly improves clinical detection and treatment prognostication.
基金：
This work was supported by the National Key
Technology R&D Program (NO. 2014BAI09B04), the
National Basic Research Program of China (973 Program)
grant (NO. 2012CB917100), the Hi-Tech Research
and Development Program of China, 863 Program
(NO. 2012AA02A201), the National Natural Science
Foundation of China, (NO. 31161130357, NO. 81172160,
and NO. 81472013), the PUMC Youth Fund and the
Fundamental Research Funds for the Central Universities
(NO. 3332013097).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|1 区医学
小类|2 区细胞生物学2 区肿瘤学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Department of Immunology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Immunology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China[15]Hubei Provincial Cooperative, Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 30068, China
医学