Analysis of intrapatient heterogeneity of circulating tumor cells at the single-cell level in the cerebrospinal fluid of a patient with metastatic gastric cancer
| Autor: | Taehyang Lee, Jang Ho Cho, Won Ki Kang, Sun Young Kim, Kyung Kim, Seung Tae Kim, Moon-Hee Sim, Jeeyun Lee |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Adenocarcinoma medicine.disease_cause Cytokeratin chemistry.chemical_compound Circulating tumor cell Cerebrospinal fluid Stomach Neoplasms Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Meningeal Neoplasms Medicine Humans Radiology Nuclear Medicine and imaging biology business.industry Gene Expression Profiling Cancer Epithelial cell adhesion molecule General Medicine Middle Aged medicine.disease Neoplastic Cells Circulating Prognosis Primary tumor Gene Expression Regulation Neoplastic Oncology chemistry biology.protein Cancer research KRAS Antibody Single-Cell Analysis business |
| Zdroj: | Journal of cancer research and therapeutics. 17(4) |
| ISSN: | 1998-4138 |
| Popis: | Background: The aims of this study were to detect circulating tumor cells (CTCs) at the single-cell level in cerebrospinal fluid (CSF) and to identify intrapatient heterogeneity of CTCs in a patient with gastric cancer (GC) with leptomeningeal metastasis (LM) using Di-Electro-Phoretic Array technology. Materials and Methods: The CSF samples were drawn from a patient who was diagnosed with GC with LM. The CSF samples were centrifuged and stained with antibody cocktail to recognize 4',6-diamidino-2-phenylindole, cytokeratin, and epithelial cell adhesion molecule (EpCAM). Gene sequencing was also conducted to evaluate the status of the gene alteration profile of CSFCTCs as compared with those of the CSF non-CTCs and the primary tumor tissue. Results: Among total 38 cells from the samples, 25 cells represented CK+ (EpCAM+), which boiled down to 0.53 CTCs in 1 mL of CSF. Each CTC was heterogeneous in terms of morphology and degree of marker expression. Some CTCs have a spindle-like shape, whereas others have a round shape. Based on molecular profiling between the 25 CK+ (EpCAM+) CTCs and 13 CK−/EpCAM− cells (i.e., the non-CTCs), CSFCTCs harbored mutations such as MDM2, TP53, KRAS, STK11, and ALK, whereas mutation of these genes was not observed in the CSF non-CTCs. Four genes of nine mutational genes totally observed in the CSFCTCs were also noted in the primary tumor tissue. Conclusions: We enriched CTCs through a single-cell sorting process in CSF samples of a GC patient with LM. We also demonstrated the intrapatient heterogeneity of the CTCs at the single-cell level. |
| Databáze: | OpenAIRE |
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