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

TL;DR

This study identifies F11R and PTGIR as new markers for mesenchymal circulating tumor cells in breast cancer, which could help improve metastasis detection and treatment.

Contribution

A new pipeline was developed to identify membrane markers in mesenchymal CTCs, leading to the discovery of F11R and PTGIR.

Findings

Hierarchical clustering isolated CTCs in the mesenchymal state from 310 samples.

F11R and PTGIR were identified as novel membrane markers with clinical significance in prognosis prediction.

The markers were validated through enriched terms, literature evidence, and molecular pathways.

Abstract

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.

•We developed a new pipeline to identify circulating tumor cell (CTC) markers of mesenchymal state in breast cancer.•A subgroup containing only CTCs in mesenchymal state was obtained by using hierarchical clustering.•We explored genes that correlated with ZEB2 and showed clinical significance, characterizing F11R and PTGIR as new markers.

We developed a new pipeline to identify circulating tumor cell (CTC) markers of mesenchymal state in breast cancer.

A subgroup containing only CTCs in mesenchymal state was obtained by using hierarchical clustering.

We explored genes that correlated with ZEB2 and showed clinical significance, characterizing F11R and PTGIR as new markers.

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