Blood Test Detects Brain Metastases While Treatable

Under strict aseptic conditions, 10 to 30 mL peripheral blood was obtained (first 5 ml were not used to avoid possible contamination by normal skin cells) and stored in tubes containing CellSave or EDTA, depending on downstream application.

For multi-parametric flow cytometry and Silicon Biosystems’ DEPArray, various primary antibodies were used. For Epithelial cell adhesion molecule (EpCAM)-positive circulating tumor cells (CTC) capture and enumeration by CellSearch, 7.5 mL of peripheral blood was collected in CellSave tubes per CTC assay procedures, and was processed using the Silicon Biosystems’ Cellsearch platform. For CTC isolation by multi-parametric flow cytometry, peripheral blood from breast cancer patients was analyzed and sorted using the FACSAriaII. The scientists also performed immuno-cytochemistry, genomic and mRNA characterization of isolated CTCs, RNA microarrays and pathway analyses.

The investigators found that breast cancer brain metastasis (BCBM) CTCs is enriched in a distinct sub-population of cells identifiable by their biomarker expression and mutational content. Deriving from a comprehensive analysis of CTC transcriptomes, they discovered a unique “circulating tumor cell gene signature” that is distinct from primary breast cancer tissues. Further dissection of the circulating tumor cell gene signature identified signaling pathways associated with BCBM CTCs that may have roles in potentiating BCBM.

Dario Marchetti, PhD, the senior author of the study, said, “Our lab is the first in this field to perform a comprehensive report of patient-derived circulating tumor cells at the gene expression level, so we now have a clearer picture of the signaling pathways that allows them to establish brain metastases. By comparing the whole genome expression patterns of CTCs isolated from patient blood samples diagnosed with or without BCBM, we uncovered a 126 gene-signature that is specific to these brain metastatic CTCs.” The study was published on August 4, 2017, in the journal Nature Communications.

Related Links:
Houston Methodist Hospital