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Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis

  • Authors:
    • Linglin Zou
    • Saber Imani
    • Mazaher Maghsoudloo
    • Marzieh Dehghan Shasaltaneh
    • Lanyang Gao
    • Jia Zhou
    • Qinglian Wen
    • Shuya Liu
    • Leisheng Zhang
    • Gang Chen
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran 1417614411, Iran, Department of Biology, Faculty of Science, University of Zanjan, Zanjan 4537138791, Iran, Sichuan Provincial Center for Gynaecology and Breast Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, School of Humanities and Management Science, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, The Postdoctoral Research Station, School of Medicine, Nankai University, Tianjin 300071, P.R. China, Department of Medical Equipment, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
    Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1075-1093
    |
    Published online on: June 18, 2020
       https://doi.org/10.3892/or.2020.7650
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Abstract

The genome‑wide copy number analysis of circulating tumor cells (CTCs) provides a promising prognostic biomarker for survival in breast cancer liver metastasis (BCLM) patients. The present study aimed to confirm the prognostic value of the presence of CTCs in BCLM patients. We previously developed an assay for the genome‑wide pattern differences in copy number variations (CNVs) as an adjunct test for the routine imaging and histopathologic diagnosis methods to distinguish newly diagnosed liver metastases and recurrent liver metastases. Forty‑three breast cancer patients were selected for this study in which 23 newly diagnosed and 20 recurrent liver metastases were diagnosed by histopathology and 18F‑FDG PET/CT imaging. CTCs were counted from all patients using the CellSearch system and were confirmed by cytomorphology and three‑color immunocytochemistry. Genomic DNA of single CTCs was amplified using multiple annealing and looping based amplification cycles (MALBAC). Then, we compared the CTC numbers of newly diagnosed and recurrent BCLM patients using Illumina platforms. A high CTC frequency (>15 CTCs/7.5 ml blood) was found to be correlated with disease severity and metastatic progression, which suggests the value for CTCs in the diagnosis of BCLM in comparison with pathohistology and PET/CT imaging (P>0.05). Moreover, CTCs isolated from BCLM patients remained an independent prognostic detection factor associated with overall survival (P=0.0041). Comparison between newly diagnosed and recurrent liver metastases revealed different frequencies of CNVs (P>0.05). Notably, the CNV pattern of isolated CTCs of recurrent BCLM patients was similar to recurrent liver metastases (nearly 82% of the gain/loss regions). Functional enrichment analysis identified 25 genes as a CNV signature of BCLM. Among them, were defensin and β‑defensin genes, which are significantly associated with anti‑angiogenesis and immunomodulation signaling pathways. High CTC frequencies are effective in the evaluation and differentiation between newly diagnosed liver metastases from recurrent liver metastases. Future clinical studies will be necessary to fully determine the prognostic potential of CTC cluster signatures in patients with BCLM.
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Copy and paste a formatted citation
Spandidos Publications style
Zou L, Imani S, Maghsoudloo M, Shasaltaneh MD, Gao L, Zhou J, Wen Q, Liu S, Zhang L, Chen G, Chen G, et al: Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis. Oncol Rep 44: 1075-1093, 2020.
APA
Zou, L., Imani, S., Maghsoudloo, M., Shasaltaneh, M.D., Gao, L., Zhou, J. ... Chen, G. (2020). Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis. Oncology Reports, 44, 1075-1093. https://doi.org/10.3892/or.2020.7650
MLA
Zou, L., Imani, S., Maghsoudloo, M., Shasaltaneh, M. D., Gao, L., Zhou, J., Wen, Q., Liu, S., Zhang, L., Chen, G."Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis". Oncology Reports 44.3 (2020): 1075-1093.
Chicago
Zou, L., Imani, S., Maghsoudloo, M., Shasaltaneh, M. D., Gao, L., Zhou, J., Wen, Q., Liu, S., Zhang, L., Chen, G."Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis". Oncology Reports 44, no. 3 (2020): 1075-1093. https://doi.org/10.3892/or.2020.7650
Copy and paste a formatted citation
x
Spandidos Publications style
Zou L, Imani S, Maghsoudloo M, Shasaltaneh MD, Gao L, Zhou J, Wen Q, Liu S, Zhang L, Chen G, Chen G, et al: Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis. Oncol Rep 44: 1075-1093, 2020.
APA
Zou, L., Imani, S., Maghsoudloo, M., Shasaltaneh, M.D., Gao, L., Zhou, J. ... Chen, G. (2020). Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis. Oncology Reports, 44, 1075-1093. https://doi.org/10.3892/or.2020.7650
MLA
Zou, L., Imani, S., Maghsoudloo, M., Shasaltaneh, M. D., Gao, L., Zhou, J., Wen, Q., Liu, S., Zhang, L., Chen, G."Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis". Oncology Reports 44.3 (2020): 1075-1093.
Chicago
Zou, L., Imani, S., Maghsoudloo, M., Shasaltaneh, M. D., Gao, L., Zhou, J., Wen, Q., Liu, S., Zhang, L., Chen, G."Genome‑wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis". Oncology Reports 44, no. 3 (2020): 1075-1093. https://doi.org/10.3892/or.2020.7650
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