Identification of novel membrane markers in circulating tumor cells of mesenchymal state in breast cancer.

Cancer metastasis is a major cause of cancer-related deaths worldwide. The ability to detect and monitor circulating tumor cells (CTCs) offers a promising approach to early detection and management of metastasis. Although studies on epithelial markers for CTC detection are actively underway, the discovery of mesenchymal markers has not been studied sufficiently. In this study, we developed a new pipeline to identify membrane markers in CTCs of mesenchymal state in breast cancer based on expression profiles of the 310 CTC samples. From the total CTC samples, only CTC samples in the mesenchymal state were collected by employing hierarchical clustering. In samples belonging to the mesenchymal state, we calculated the correlation coefficients between 1995 membrane genes and ZEB2, which was determined as the key mesenchymal signature, allowing the 84 positively correlated genes. Furthermore, to ensure clinical significance, Kaplan-Meier analysis were performed on the 124 breast cancer patients, resulting in the 14 genes predicting prognosis. By exploring genes commonly identified in the both analyses, F11R and PTGIR were characterized as membrane markers in CTCs of mesenchymal state in breast cancer, which were evaluated by enriched terms, literature evidence, and relevant molecular pathways. We expect that the results will be helpful to more effective strategies for metastasis management.