Prognostic Value of Novel Liquid Biomarkers in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: A Prospective Observational Study

被引：34

作者：

Benoist, Guillemette E. ^{[1
]}

van Oort, Inge M. ^{[2
]}

Boerrigter, Emmy ^{[1
]}

Verhaegh, Gerald W. ^{[2
]}

van Hooij, Onno ^{[2
]}

Groen, Levi ^{[2
]}

Smit, Frank ^{[3
]}

de Mol, Pieter ^{[4
]}

Hamberg, Paul ^{[5
]}

Dezentje, Vincent O. ^{[6
]}

Mehra, Niven ^{[7
]}

Gerritsen, Winald ^{[7
]}

Somford, Diederik M. ^{[8
]}

van Erp, Nielka P. H. ^{[1
]}

Schalken, Jack A. ^{[2
]}

机构：

[1] Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Dept Urol, Med Ctr, Nijmegen, Netherlands

[3] MDxHlth, Nijmegen, Netherlands

[4] Gelderse Vallei Hosp, Dept Med Oncol, Ede, Netherlands

[5] Franciscus Gasthuis & Vlietland, Dept Med Oncol, Rotterdam, Netherlands

[6] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands

[7] Radboud Univ Nijmegen, Dept Med Oncol, Med Ctr, Nijmegen, Netherlands

[8] Canisius Wilhelmina Hosp, Dept Urol, Nijmegen, Netherlands

来源：

CLINICAL CHEMISTRY | 2020年 / 66卷 / 06期

关键词：

SPLICE VARIANT 7; CIRCULATING MICRORNAS; INCREASED SURVIVAL; WHOLE-BLOOD; ABIRATERONE; EXPRESSION; TMPRSS2-ERG; THERAPY; MIR-375; MIR-141;

D O I：

10.1093/clinchem/hvaa095

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

BACKGROUND: Several treatment options were recently added for metastatic castration-resistant prostate cancer (mCRPC). However, response to therapy is variable, and biomarkers that can guide treatment selection and response evaluation are lacking. Circulating RNAs are a promising source of biomarkers. We explored messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) as potential biomarkers in liquid biopsies of patients with mCRPC treated with enzalutamide. METHODS: Forty patients were included in this prospective multicenter observational study. Whole blood was drawn at baseline and 1, 3, and 6 months after start of therapy. Four mRNAs, 6 miRNAs, and 5 lncRNAs were analyzed by quantitative PCR. RNA levels in 30 healthy individuals were used as controls. RNA expression data were analyzed by Kaplan-Meier and Cox regression analyses, and the primary end point was progression-free survival. Clinical factors were included in the multivariable Cox regression analysis. RESULTS: Levels of 2 miRNAs, miR-375 and miR-3687, and 1 lncRNA, N-acetylated alpha-linked acidic dipeptidase like 2 antisense RNA 2 (NAALADL2-AS2), were more than 2-fold higher in patients with mCRPC compared with healthy volunteers. Patients with higher levels of miR-375 or miR-3687 showed a shorter time to progression. Patients with higher levels of NAALADL2-AS2 showed a longer time to progression. In the multivariable Cox regression analysis, higher miR-375, miR-3687 and serum prostate-specific antigen concentrations were shown to be independent predictors for shorter time to progression. CONCLUSIONS: We identified miR-3687 as a novel prognostic marker for response in patients with CRPC treated with enzalutamide, and we confirmed the prognostic value of miR-375.

引用

页码：842 / 851

页数：10

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