Circulating miRNAs are correlated with tumor progression in prostate cancer.
Circulating miRNAs have recently been indicated as practicable and promising biomarkers for noninvasive diagnosis in various tumor entities. However, cell-free miRNAs have not been found to correlate with clinicopathological variables in epithelial carcinomas. To learn more about the potential clinical relevance of circulating miRNAs in prostate cancer, we screened 667 miRNAs in serum samples from patients with metastatic (n = 7) and localized prostate cancer (n = 14). Various miRNAs were highly abundant in the sera of patients with metastatic disease, and five upregulated miRNAs (miRNA-375, miRNA-9*, miRNA-141, miRNA-200b and miRNA-516a-3p) were selected for further validation. In the first validation study (n = 45), selected miRNAs were analyzed in a prospectively collected serum set taken from different prostate cancer risk groups. Most of the selected miRNAs were significantly correlated with adverse risk factors when different clinicopathological variables were analyzed. Circulating miRNA-375 and miRNA-141 turned out to be the most pronounced markers for high-risk tumors. Their levels also correlated with high Gleason score or lymph-node positive status in a second independent validation study (n = 71). In addition, the expression levels of miRNA-375 and miRNA-141 were monitored in 72 prostate tissue samples (36 tumor vs. 36 benign). Both miRNAs were highly expressed in all samples and significantly upregulated in the tumors compared to normal tissues. Overall, our observations suggest that miRNA-375 and miRNA-141 expression is enhanced in prostate cancer specimens and their release into the blood is further associated with advanced cancer disease.
Brase
Jan C
JC
Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany. j.brase@dkfz.de
Johannes
Marc
M
Schlomm
Thorsten
T
Fälth
Maria
M
Haese
Alexander
A
Steuber
Thomas
T
Beissbarth
Tim
T
Kuner
Ruprecht
R
Sültmann
Holger
H
D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D012313:RNA / Q000097:blood / Q000302:isolation & purification; D015203:Reproducibility of Results
D035683:MicroRNAs; D012313:RNA; D017430:Prostate-Specific Antigen