Oncotarget

Clinical Research Papers:

Clinical significance of phenotyping and karyotyping of circulating tumor cells in patients with advanced gastric cancer

Yilin Li, Xiaotian Zhang, Sai Ge, Jing Gao, Jifang Gong, Ming Lu, Qiyue Zhang, Yanshuo Cao, Daisy Dandan Wang, Peter Ping Lin and Lin Shen _

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Oncotarget. 2014; 5:6594-6602. https://doi.org/10.18632/oncotarget.2175

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Abstract

Yilin Li1, Xiaotian Zhang1, Sai Ge1, Jing Gao1, Jifang Gong1, Ming Lu1, Qiyue Zhang1, Yanshuo Cao1, Daisy Dandan Wang2, Peter Ping Lin2, Lin Shen1

1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, Peking University Cancer Hospital & Institute, Beijing, China

2 Cytelligen, San Diego, CA, USA

Correspondence:

Lin Shen, email:

Keywords: gastric cancer, circulating tumor cells, EpCAM-independent enrichment, HER2, aneuploidy

Received: May 20, 2014 Accepted: July 05, 2014 Published: July 07, 2014

Abstract

BACKGROUND: Karyotyping and phenotyping of circulating tumor cells (CTCs) in therapeutic cancer patients is of particular clinical significance in terms of both identifying chemo-resistant CTC subtypes and understanding CTC evolution.

METHODS: The integrated subtraction enrichment (SET) and immunostaining-fluorescence in situ hybridization (iFISH) platform was applied to detect and characterize CTCs in patients with advanced gastric cancer (AGC). Status of human epidermal growth factor receptor 2 (HER2) expressing and aneuploidy of chromosome 8 in CTCs enriched from the patients was examined by SET-iFISH following clinical chemotherapy or HER2-targeted therapy. CellSearch system was applied as a reference control.

RESULTS: Phenotyping of CTCs in HER2 positive AGC patients demonstrated that HER2+ CTCs could be effectively eliminated in response to HER2-targeted therapy. Karyotyping of CTCs indicated that distinct CTCs with different ploidies of chromosomes 8 in AGC patients correlated to either sensitivity or resistance of paclitaxel or cisplatin-based chemotherapy. Examination of the copy number of chromosome 8 in CTCs provides a potential approach for predicting chemotherapeutic efficacy and monitoring chemo-resistance.

CONCLUSIONS: Phenotyping and karyotyping of the enriched CTCs upon ploidy of chromosome 8 or HER2 expression is of clinical potential for monitoring chemo-resistance and evaluating therapeutic efficacy for AGC patients.


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