Journal
ONCOTARGET
Volume 5, Issue 16, Pages 6594-6602Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2175
Keywords
gastric cancer; circulating tumor cells; EpCAM-independent enrichment; HER2; aneuploidy
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Funding
- NSFC [81301323, 81172110]
- National High Technology Research and Development Program of China [2012AA 02A 504]
- Beijing Municipal Science & Technology Commission Program [Z11110706730000]
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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 chemoresistance and evaluating therapeutic efficacy for AGC patients.
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