Expression of tumour progression-associated genes in circulating tumour cells of patients at different stages of prostate cancer

Abstract

Objective: To evaluate the presence of circulating tumour cells (CTCs) at different stages of prostate cancer using the AdnaTest^® ProstateCancerDetect kit (Qiagen). Moreover, we aimed to assess the expression of transcripts that are specific for cancer stem cells (AdnaTest StemCell) and epithelial-mesenchymal transition (EMT) in CTCs (AdnaTest EMT), as well as additional genes that are known to promote prostate cancer progression.

Patients and methods: In this prospective study, we included 81 patients who underwent treatment for prostate cancer between 07/2014 and 02/2015, including: Group A, 18 patients (22.2%) with low-risk clinically localised prostate cancer; Group B, 25 patients (30.9%) with high-risk clinically localised prostate cancer; Group C, 11 patients (13.6%) with metastatic castration-sensitive prostate cancer (mCSPC); and Group D, 27 patients (33.3%) with metastatic castration-resistant prostate cancer (mCRPC). AdnaTest ProstateCancer and AdnaTest StemCell/EMT were performed in all cases. In addition, expression of the androgen receptor (AR), c-met, c-kit and thymidylate synthase (TYMS) in CTCs was assessed using specific polymerase chain reaction assays.

Results: A positive AdnaTest ProstateCancer was present in three (16.7%), two (8.0%), six (54.5%) and 19 (70.5%) patients in groups A, B, C and D, respectively (P < 0.01, chi-squared test). The AdnaTest EMT and AdnaTest StemCell were positive in zero (0.0%), zero (0.0%), one (9.1%), and two (7.4%); and in five (27.8%), four (16.0%), three (27.3%), and 11 (40.7%) patients in groups A, B, C and D, respectively, with no significant differences noted between groups. CTCs expressing TYMS (44.4% and 50.0% vs 13.9%) or AR (18.2% and 25.9% vs 0.0%) were seen more commonly in patients in groups C and D vs patients with non-metastatic disease (all P < 0.05). Expression of c-kit and c-met were rare events, with only two patients positive for either marker.

Conclusions: AdnaTest ProstateCancerDetect exhibits positive results mainly in patients with metastatic disease. Expression of AR and TYMS are frequent events in CTCs of patients with advanced disease, whereas c-met and c-kit gene expression is seen in only a small proportion of patients. The implications of these results for the use of CTC analysis as a decision factor for personalised treatment strategies in advanced prostate cancer remain to be determined.

Keywords: #PCSM; #ProstateCancer; AdnaTest®; circulating tumour cells; epithelial mesenchymal transition; prostate cancer; stem cell.