Circulating RNAs extracted from liquid biopsies represent a promising source of cancer and therapy-related biomarkers. We screened whole blood from patients with metastatic castration-resistant prostate cancer (mCRPC) following their first-line treatment with abiraterone acetate and prednisone (AA-P) to identify circulating RNAs that may correlate with progression free survival (PFS). In a prospective multi-center observational study, 53 patients with mCRPC were included after they started first-line AA-P treatment. Blood was drawn at baseline, one, three and six months after treatment initiation. The levels of pre-defined circulating RNAs earlier identified as being upregulated in patients with mCRPC (e.g. microRNAs, long non-coding RNAs and messenger RNAs), were analyzed. Uni- and multi-variable Cox regression and Kaplan-Meier analyses were used to analyze the prognostic value of the various circulating RNAs for PFS along treatment. Detectable levels of KLK3 mRNA at baseline were demonstrated to be an independent prognostic marker for PFS (201 vs 501 days, P=0.00054). Three months after AA-P treatment initiation, KLK3 could not be detected in the blood of responding patients, but was still detectable in 56% of the patients with early progression. Our study confirmed that KLK3 mRNA detection in whole blood is an independent prognostic marker in mCRPC patients receiving AA-P treatment. Furthermore, the levels of circulating KLK3 mRNA in patients receiving AA-P treatment might reflect treatment response or early signs of progression.
Molecular oncology. 2021 Mar 02 [Epub ahead of print]
E Boerrigter, G E Benoist, I M van Oort, G W Verhaegh, O van Hooij, L Groen, F Smit, I M Oving, P de Mol, T J Smilde, D M Somford, N Mehra, J A Schalken, N P van Erp
Department of Pharmacy, Radboud university medical center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Department of Urology, Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands., MDxHealth, Nijmegen, The Netherlands., Department of Medical Oncology, Ziekenhuisgroep Twente, Almelo, The Netherlands., Department of Medical Oncology, Gelderse Vallei Hospital, Ede, The Netherlands., Department of Medical Oncology, Jeroen Bosch Hospital, Hertogenbosch, The Netherlands., Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands., Deparment of Medical Oncology, Radboud university medical center, Nijmegen, The Netherlands.