| Autor: |
Bjerre MT; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. mtbjerre@clin.au.dk (M.T.B.).; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.; Department of Urology, Aarhus University Hospital, 8200 Aarhus N, Denmark.; Department of Urology, Regional Hospital West Jutland, 7500 Holstebro, Denmark., Nørgaard M; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. mtbjerre@clin.au.dk (M.T.B.).; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Larsen OH; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. mtbjerre@clin.au.dk (M.T.B.).; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Jensen SØ; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. mtbjerre@clin.au.dk (M.T.B.).; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Strand SH; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. mtbjerre@clin.au.dk (M.T.B.).; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Østergren P; Department of Urology, Herlev andGentofte Hospital, 2730 Herlev, Denmark peter.busch.oestergren@regionh.dk (P.Ø.)., Fode M; Department of Urology, Herlev andGentofte Hospital, 2730 Herlev, Denmark peter.busch.oestergren@regionh.dk (P.Ø.)., Fredsøe J; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. mtbjerre@clin.au.dk (M.T.B.).; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Ulhøi BP; Department of Pathology, Aarhus University Hospital, 8200 Aarhus N, Denmark. beneulho@rm.dk., Mortensen MM; Department of Urology, Aarhus University Hospital, 8200 Aarhus N, Denmark., Jensen JB; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.; Department of Urology, Regional Hospital West Jutland, 7500 Holstebro, Denmark., Borre M; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.; Department of Urology, Aarhus University Hospital, 8200 Aarhus N, Denmark., Sørensen KD; Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. mtbjerre@clin.au.dk (M.T.B.).; Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark. |
| Abstrakt: |
Novel and minimally-invasive prostate cancer (PCa)-specific biomarkers are needed to improve diagnosis and risk stratification. Here, we investigated the biomarker potential in localized and de novo metastatic PCa (mPCa) of methylated circulating tumor DNA (ctDNA) in plasma. Using the Marmal-aid database and in-house datasets, we identified three top candidates specifically hypermethylated in PCa tissue: DOCK2, HAPLN3, and FBXO30 (specificity/sensitivity: 80%-100%/75-94%). These candidates were further analyzed in plasma samples from 36 healthy controls, 61 benign prostatic hyperplasia (BPH), 102 localized PCa, and 65 de novo mPCa patients using methylation-specific droplet digital PCR. Methylated ctDNA for DOCK2/HAPLN3/FBXO30 was generally not detected in healthy controls, BPH patients, nor in patients with localized PCa despite a positive signal in 98%-100% of matched radical prostatectomy tissue samples. However, ctDNA methylation of DOCK2, HAPLN3, and/or FBXO30 was detected in 61.5% (40/65) of de novo mPCa patients and markedly increased in high- compared to low-volume mPCa (89.3% (25/28) vs. 32.1% (10/31), p < 0.001). Moreover, detection of methylated ctDNA was associated with significantly shorter time to progression to metastatic castration resistant PCa, independent of tumor-volume. These results indicate that methylated ctDNA ( DOCK2/HAPLN3/FBXO30 ) may be potentially useful for identification of hormone-naïve mPCa patients who could benefit from intensified treatment. |
