Autor: |
John W.M. Martens, John A. Foekens, Stefan Sleijfer, Jan W. Gratama, Yixin Wang, John Jiang, Jack X. Yu, Marcel Smid, Carolien H.M. van Deurzen, Raquel Ramírez-Moreno, Petra van der Spoel, Jaco Kraan, Vanja de Weerd, Anne Van Galen, Peter A. van Dam, Luc Y. Dirix, Jacqueline M.L. Stouthard, Felix E. de Jongh, Dieter Peeters, Joan Bolt-de Vries, Bianca Mostert, Anieta M. Sieuwerts |
Rok vydání: |
2023 |
DOI: |
10.1158/1078-0432.c.6519192.v1 |
Popis: |
Purpose: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer.Experimental Design: CTCs were isolated with the epithelial cell adhesion molecule–based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors.Results: We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels.Conclusions: Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs. Clin Cancer Res; 17(11); 3600–18. ©2011 AACR. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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