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KLK3, PCA3, and TMPRSS2-ERG expression in the peripheral blood mononuclear cell fraction from castration-resistant prostate cancer patients and response to docetaxel treatment.
- Source :
-
The Prostate [Prostate] 2014 Sep; Vol. 74 (12), pp. 1222-30. Date of Electronic Publication: 2014 Jul 07. - Publication Year :
- 2014
-
Abstract
- Background: To monitor systemic disease activity, the potential of circulating tumor cells (CTCs) bears great promise. As surrogate for CTCs we measured KLK3, PCA3, and TMPRSS2-ERG messenger RNA (mRNA) in the peripheral blood mononuclear cell (PBMC) fraction from a castration-resistant prostate cancer (CRPC) patient cohort and three control groups. Moreover, biomarker response to docetaxel treatment was evaluated in the patient group.<br />Methods: Blood samples from 20 CRPC patients were analyzed at four different time points (prior to docetaxel treatment, at 9 weeks, 27 weeks, and 2 months after treatment). Blood was drawn once from three control groups (10 age-matched men, 10 men under 35 years of age, 12 women). All samples were analyzed for KLK3, PCA3, and TMPRSS2-ERG mRNA by using a quantitative nucleic acid amplification assay with gene-specific primers in the complementary DNA synthesis.<br />Results: At baseline, mRNA for KLK3 was detected in 17 (89%, 95% CI 76-100%), PCA3 in 10 (53%, 95% CI 30-75%), and TMPRSS2-ERG in seven of 19 evaluable patients (37%, 95% CI 15-59%). In contrast, the blood samples from all 32 healthy volunteers were reproducible negative for all markers. In response to docetaxel treatment, KLK3 levels decreased in 80% (95% CI 60-100%), PCA3 in 89% (95% CI 68-100%), and TMPRSS2-ERG in 86% (95% CI 60-100%) of patients.<br />Conclusions: The feasibility of a highly sensitive modified nucleic acid amplification assay to assess KLK3, PCA3, and TMPRSS2-ERG mRNA in the PBMC fraction from CRPC patients was demonstrated. Moreover, response of these markers to systemic treatment was shown.<br /> (© 2014 Wiley Periodicals, Inc.)
- Subjects :
- Adult
Aged
Antigens, Neoplasm biosynthesis
Biomarkers, Tumor biosynthesis
Docetaxel
Female
Humans
Kallikreins biosynthesis
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear metabolism
Leukocytes, Mononuclear pathology
Longitudinal Studies
Male
Middle Aged
Nucleic Acid Hybridization
Oncogene Proteins, Fusion biosynthesis
Prospective Studies
Prostate-Specific Antigen biosynthesis
Prostatic Neoplasms, Castration-Resistant metabolism
RNA, Messenger biosynthesis
Treatment Outcome
Young Adult
Antigens, Neoplasm genetics
Biomarkers, Tumor genetics
Gene Expression Regulation, Neoplastic drug effects
Kallikreins genetics
Oncogene Proteins, Fusion genetics
Prostate-Specific Antigen genetics
Prostatic Neoplasms, Castration-Resistant drug therapy
Prostatic Neoplasms, Castration-Resistant genetics
Taxoids therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0045
- Volume :
- 74
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 25043536
- Full Text :
- https://doi.org/10.1002/pros.22839