Abstract
Abstract Lung cancer is the most common cancer, which also leading cause of global cancer mortality. Metastasis is a complex multi-step process that represents the most deadly aspect of cancer. One key step in metastasis is the entry of circulating tumor cells (CTCs) into secondary or distant organ sites to become disseminated tumor cells for subsequent metastasis. Exosomes, a subset of extracellular vesicles (EVs), function as a mode of intercellular communication and molecular transfer. Tumor cells are avid producers of exosomes, and tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. The aim of this pilot study is to investigate the relationship between the count of circulating tumor cells in peripheral blood and the clinical stage of lung cancer, and the difference between normal (healthy) person exosomes and cancer patients exosomes in the rate of exosomes release and the content (most notably proteins). A total of 140 patients participated in the project and twelve blood samples from healthy volunteers were also collected in the Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. After obtaining the informed consent, blood samples (5 ml) were stored in the ACD anticoagulant tube. CTCs was counted by immunomagnetic beads negative enrichment technique combined with immunofluorescence staining of chromosome in situ hybridization. The correlation between the count of CTCs and the clinical stage was analyzed. Exosomes were isolated by Density Gradient (DG) centrifugation. Exosomes concentration and size was analyzed by Nanoparticle Tracking Analysis (NTA), and protein was analyzed by HPLC-CHIP-MS/MS. In 114 patients, the positive rate of CTCs was 93.86% (in 3.2mL blood CTCs≥1, 107/114). The count of CTCs was negatively correlated with clinical stage (rs=-0.279, p=0.003), which suggest that CTCs is highly expressed in early lung cancer patients. Exosomes test results showed that there was a significant difference between lung cancer patients and healthy person. The size of exosome in healthy person was significantly smaller and the concentration was significantly higher when compared with lung cancer patients (p<0.05). In addition, the mass spectrometry results showed that the control group had 135 proteins in the exosomes, while the patient group contained 167 proteins, which 89 proteins were shared with each other. These results suggest that CTCs plays an important role in the pathogenesis of lung cancer and should be a target for early postoperative metastasis. The analysis of exosomes in NSCLC could represent a noninvasive test for assess disease progression. Citation Format: Zujun Que, Yi Jiang, Fangfang Qian, Zhi Qiao, Hua Xiao, Lingshuang Liu, Hegen Li, Jianhui Tian. Correlation of exosomes and CTCs in non-small cell lung cancer patients with disease stage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1577.
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