Targeted RNA-seq signature of Breast Cancer Circulating Tumor Cells correlates with occurrence of bone-only metastases

Bone is the most frequent site of metastases from breast cancer (BC), although no biomarkers are yet available to predict the risk of skeletal dissemination. Here, we attempted to identify a gene signature correlated with bone metastasis (BM) onset in circulating tumor cells (CTCs) isolated from 40 metastatic BC patients, grouped according to their metastasis sites at the time of enrollment, namely “BM” (bone-only), “ES” (extra-skeletal) or “BM+ES” (bone and extra-skeletal). A 134-gene panel, derived from an extensive literature review, was validated on sub-clones of the MDA-MB-231 BC cell line with variable organotropism and then applied to CTC groups for targeted RNA sequencing. No correlation was found between CTC number and clinico-pathologic variables, whereas 31 differentially expressed genes emerged from “BM” and “ES” CTC comparison. The putative prognostic meaning of the “top-10” most deregulated genes was finally explored and pointed out by employing an external BC dataset. Targeted RNA-seq of circulating tumor cells (CTCs) isolated from 40 metastatic BC patients.