Bone is the most frequent site of metastases from breast cancer (BC), but no biomarkers are yet available to predict skeletal dissemination.
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).
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.
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.
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The datasets generated during this study are available at Gene Expression Omnibus (GEO) data repository, with GEO accession number GSE160314.
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The authors are grateful to Luigia Stefania Stucci for her precious help in recruiting participants and to Claudia Felici for her valuable technical support. The authors would like to thank also “DIVELLA SpA” and particularly Enzo Divella, for the generous donation of the Ion Torrent used for NGS analyses.
This work was supported by the Apulia Region (“Oncogenomic”, “Jonico-Salentino”, “Precision Medicine” and “Tecnopolo per la Medicina di Precisione-GR Puglia 2117/2018” projects).
Ethics approval and consent to participate
The patients were enrolled after written informed consent. The study was approved by the Ethics Committee of the University Hospital “Policlinico of Bari” (Project identification code: 44100) and performed in accordance with the principles of the Declaration of Helsinki.
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JB: speaker fees from Amgen and advisory board Novartis; DL, SD, RP, PC, SW, CP, EL, RC and FS declare no competing interests.
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Lovero, D., D’Oronzo, S., Palmirotta, R. et al. Correlation between targeted RNAseq signature of breast cancer CTCs and onset of bone-only metastases. Br J Cancer (2021). https://doi.org/10.1038/s41416-021-01481-z