Post-treatment circulating plasma BMP6 mRNA and H3K27 methylation levels discriminate metastatic prostate cancer from localized disease.
BACKGROUND
We evaluated the utility of post-treatment plasma levels of the circulating bone-morphogenetic protein-6-specific mRNA (cBMP6 mRNA), cell-free DNA (cf-DNA), apoptotic nucleosomes and Histone H3 lysine 27 trimethylation (H3K27me3), in discriminating metastatic prostate cancer (PCa) from organ confined, locally controlled disease.


METHODS
Peripheral blood was taken from the patients at the end of therapy, and quantitative PCR was performed to amplify cBMP6 mRNA or cf-DNA from plasma while apoptotic nucleosomes and H3K27me3 were determined by ELISA-based approaches. Following blinded measurements, the markers were compared between the patients with local (n=22), local advanced (n=11) or metastatic disease (n=28).


RESULTS
Of the four markers investigated, the cBMP6 mRNA and H3K27me3 levels revealed significant differences between the three subgroups. We found higher levels of cBMP6 mRNA in the patients with metastases than in those with localized (p=0.001) or local advanced disease (p=0.05). When compared to cBMP6, H3K27me3 displayed an inverse distribution and was significantly lower in the patients with metastatic disease than in those with localized (p=0.05) or local advanced disease (p=0.024). There was no correlation between the different markers and total PSA levels or Gleason score at diagnosis.


CONCLUSIONS
Our study provides evidence that post-treatment analysis of cBMP6 mRNA and H3K27me3 may be used to distinguish metastatic PCa from organ confined, locally controlled disease.
Deligezer
Ugur
U
Istanbul University Oncology Institute, Department of Basic Oncology, Istanbul, Turkey. ugur_deligezer@yahoo.com
Yaman
Fulya
F
Darendeliler
Emin
E
Dizdar
Yavuz
Y
Holdenrieder
Stefan
S
Kovancilar
Müge
M
Dalay
Nejat
N
D000368:Aged; D015415:Biomarkers / Q000097:blood; D055418:Bone Morphogenetic Protein 6 / Q000097:blood / Q000235:genetics*; D003937:Diagnosis, Differential; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008745:Methylation; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009367:Neoplasm Staging / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000097:blood*
D015415:Biomarkers; D055418:Bone Morphogenetic Protein 6; D006657:Histones; D012333:RNA, Messenger