Correlation between targeted RNAseq signature of breast cancer CTCs and onset of bone-only metastases

Background Bone is the most frequent site of metastases from breast cancer (BC), but no biomarkers are yet available to predict skeletal dissemination. Methods We attempted to identify a gene signature correlated with bone metastasis (BM) onset in circulating tumour cells (CTCs), isolated by a DEPArray-based protocol from 40 metastatic BC patients and grouped according to metastasis sites, namely BM (bone-only), ES (extra-skeletal) or BM + ES (bone + extra-skeletal). Results A 134-gene panel was first validated through targeted RNA sequencing (RNAseq) on sub-clones of the MDA-MB-231 BC cell line with variable organotropism, which successfully shaped their clustering. The panel was then applied to CTC groups and, in particular, the BM vs ES CTC comparison revealed 31 differentially expressed genes, including MAF, CAPG, GIPC1 and IL1B, playing key prognostic roles in BC. Conclusion Such evidence confirms that CTCs are suitable biological sources for organotropism investigation through targeted RNAseq and might deserve future applications in wide-scale prospective studies.

Automated summary

The study identified a gene signature correlated with bone metastasis in circulating tumor cells isolated from metastatic breast cancer patients, and revealed 31 differentially expressed genes in CTCs, including MAF, CAPG, GIPC1, and IL1B, which play key prognostic roles in breast cancer.