Disseminated tumor cells in bone marrow as predictive classifiers for small cell lung cancer patients  

作　　者：Ying Wang Jingying Nong Baohua Lu Yuan Gao Mingming Hu Cen Chen Lina Zhang Jinjing Tan Xiaomei Yang Peter Ping Lin Xingsheng Hu Tongmei Zhang 

机构地区：[1]Department of Medical Oncology,Beijing Chest Hospital,Capital Medical University,Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing,China [2]Department of Thoracic Surgery,Xuanwu Hospital,Capital Medical University,Beijing,China [3]The First School of Clinical Medicine,Shaanxi University of Chinese Medicine,Xianyang,China [4]Department of Cancer Research Center,Beijing Chest Hospital,Capital Medical University,Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing,China [5]Beijing Key Laboratory for Tumor Invasion and Metastasis,Department of Biochemistry and Molecular Biology,Capital Medical University,Beijing,China [6]Joint Laboratory for Precision Diagnosis and Treatment Translational Research in Malignant Tumors,Gynecologic Oncology Basic and Clinical Research Laboratory,Capital Medical University,Beijing,China [7]Cytelligen,San Diego,USA [8]Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [9]Laboratory for Clinical Medicine,Capital Medical University,Beijing,China

出　　处：《Journal of the National Cancer Center》2024年第4期335-345,共11页癌症科学进展（英文）

基　　金：Beijing Municipal Science and Technol-ogy Commission(grant number Z211100002921013);Tongzhou Liang-gao Talents Project(grant number YH201920);Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research In-stitutes(grant number JYY2024-14);Beijing Municipal Public Wel-fare Development and Reform Pilot Project for Medical Research Insti-tutes(grant number JYY2023-15);We thank all participants and their families for supporting this study.

摘　　要：Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical signifi- cance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis re- vealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs ( P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes ( P = 0.046 and P = 0.048). Pa- tients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs ( P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progress

关 键 词：Bone marrow Aneuploid DTCs and DTECs SE-iFISH PROGNOSIS SCLC 

分 类 号：R73[医药卫生—肿瘤]