gms | German Medical Science

Background: The Parsortix size-based circulating tumor cell (CTC) enrichment system has demonstrated superior recovery rates compared to EpCAM-dependent approaches in clear cell renal carcinoma cell (ccRCC) – at least in cell line experiments. Using a cohort of ccRCC patients undergoing Cabozantinib treatment, we aimed to analyze prognosis of both CK19 expression (as marker for presence of CTC) and expression of Cabozantinib target genes.

Methods: CTC enrichment was performed using the size-based Parsortix system followed by qPCR analysis of CK19 (CTC marker), MET, AXL and KDR5 (Cabozantinib target genes). Patients were then stratified into CK19 positive, ‘any biomarker’ positive or ‘MET only’ positive subgroups. Finally, subgroups were analyzed for correlation with progression-free survival (PFS) and overall survival (OS).

Results: Of 37 patients, 13 (35.1%), 9 (24.3%), 7 (18.9%) and 5 (13.5%) were found to be CK19 positive, ‘any biomarker’ (AXL, MET or KDR), ‘AXL/MET positive’ or ‘MET only’ positive, respectively. No differences were detected between CK19 positive and negative subgroups with respect to PFS and OS. Additionally, PFS were similar between ‘any biomarker’ and ‘MET only’ subgroups. Nonetheless, we observed differences in OS in ‘any biomarker’ and ‘MET only’ subgroups; although not statistically significant.

Conclusion: Our study revealed the ability of size-based CK19+ cells, presumably CTC enrichment along with drug target gene expression analysis in ccRCC patients. Still, cohort size of this study is too small in order to draw significant conclusions. However, given that qPCR analysis does not clearly demonstrate presence or absence of CTC, future studies might imply more pronounced proteomic or cellular analysis of CTCs. Further studies are required to analyze correlation between drug target gene expression and clinical outcome.