title: Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer.
abstract: Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and response to treatment.
authors.affiliation: Veridex/Ortho-Clinical Diagnostics, Inc., Johnson & Johnson, Raritan, NJ 08869;
authors.forename: Haiying
authors.initials: H
authors.lastname: Wang
authors.affiliation: Departments of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Molina
authors.affiliation: Veridex/Ortho-Clinical Diagnostics, Inc., Johnson & Johnson, Raritan, NJ 08869;
authors.forename: John
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ferber
authors.affiliation: Breast Clinic, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Pruthi
authors.affiliation: Veridex/Ortho-Clinical Diagnostics, Inc., Johnson & Johnson, Raritan, NJ 08869;
authors.forename: Timothy
authors.initials: T
authors.lastname: Jatkoe
authors.affiliation: Veridex/Ortho-Clinical Diagnostics, Inc., Johnson & Johnson, Raritan, NJ 08869;
authors.forename: Carlo
authors.initials: C
authors.lastname: Derecho
authors.affiliation: Veridex/Ortho-Clinical Diagnostics, Inc., Johnson & Johnson, Raritan, NJ 08869;
authors.forename: Yashoda
authors.initials: Y
authors.lastname: Rajpurohit
authors.affiliation: Veridex/Ortho-Clinical Diagnostics, Inc., Johnson & Johnson, Raritan, NJ 08869;
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Veridex/Ortho-Clinical Diagnostics, Inc., Johnson & Johnson, Raritan, NJ 08869;
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
keywords: bone metastasis; circulating tumor cell; estrogen receptor β; gene expression; trefoil factor 1