Liquid biopsy reveals KLK3 mRNA as a prognostic marker for progression free survival in patients with metastatic castration-resistant prostate cancer undergoing first-line abiraterone acetate and prednisone treatment.

Autor: Boerrigter E; Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands., Benoist GE; Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands., van Oort IM; Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands., Verhaegh GW; Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands., van Hooij O; Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands., Groen L; Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands., Smit F; MDxHealth, Nijmegen, the Netherlands., Oving IM; Department of Medical Oncology, Ziekenhuisgroep Twente, Almelo, the Netherlands., de Mol P; Department of Medical Oncology, Gelderse Vallei Hospital, Ede, the Netherlands., Smilde TJ; Department of Medical Oncology, Jeroen Bosch Hospital, 's Hertogenbosch, the Netherlands., Somford DM; Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands., Mehra N; Deparment of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands., Schalken JA; Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands., van Erp NP; Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2021 Sep; Vol. 15 (9), pp. 2453-2465. Date of Electronic Publication: 2021 May 29.
DOI: 10.1002/1878-0261.12933
Abstrakt: 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 multicenter observational study, 53 patients with mCRPC were included after they started first-line AA-P treatment. Blood was drawn at baseline, 1, 3, and 6 months after treatment initiation. The levels of predefined circulating RNAs earlier identified as being upregulated in patients with mCRPC (e.g., microRNAs, long noncoding RNAs, and mRNAs), were analyzed. Uni- and multivariable 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 kallikrein-related peptidase 3 (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.
(© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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