5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors

被引:5
作者
Kristensen, Gitte [1 ]
Strand, Siri H. [2 ]
Roder, Martin Andreas [1 ]
Berg, Kasper Drimer [1 ]
Toft, Birgitte Gronkaer [3 ]
Hoyer, Soren [4 ]
Borre, Michael [5 ]
Sorensen, Karina Dalsgaard [2 ]
Brasso, Klaus [1 ]
机构
[1] Univ Copenhagen, Rigshosp, Dept Urol, Copenhagen Prostate Canc Ctr, DK-2100 Copenhagen, Denmark
[2] Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
[3] Univ Copenhagen, Dept Pathol, Rigshosp, DK-2100 Copenhagen, Denmark
[4] Aarhus Univ Hosp, Dept Pathol, DK-8200 Aarhus, Denmark
[5] Aarhus Univ Hosp, Dept Urol, DK-8200 Aarhus, Denmark
关键词
prostate cancer; predictive biomarkers; radical prostatectomy; 5hmC; ERG; ACTIVE-SURVEILLANCE; PROTEIN EXPRESSION; GLOBAL; 5-HYDROXYMETHYLCYTOSINE; DNA; OUTCOMES; RISK; STRAIGHTFORWARD; REARRANGEMENT; EPIGENETICS; RECURRENCE;
D O I
10.3390/ijms20051025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5-10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF (p = 0.2 and p = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP (p = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2-2.7; p = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.
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页数:12
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共 44 条
[1]   The prostate cancer genome: Perspectives and potential (Reprinted from Urol One, vol 32, 53.e15) [J].
Barbieri, Christopher E. ;
Tomlins, Scott A. .
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 2015, 33 (02) :95-102
[2]   ERG protein expression over time: from diagnostic biopsies to radical prostatectomy specimens in clinically localised prostate cancer [J].
Berg, Kasper Drimer ;
Brasso, Klaus ;
Thomsen, Frederik Birkebaek ;
Roder, M. Andreas ;
Holten-Rossing, Henrik ;
Toft, Birgitte Gronkaer ;
Iversen, Peter ;
Vainer, Ben .
JOURNAL OF CLINICAL PATHOLOGY, 2015, 68 (10) :788-794
[3]   ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer [J].
Berg, Kasper Drimer ;
Vainer, Ben ;
Thomsen, Frederik Birkebaek ;
Roder, M. Andreas ;
Gerds, Thomas Alexander ;
Toft, Birgitte Gronkaer ;
Brasso, Klaus ;
Iversen, Peter .
EUROPEAN UROLOGY, 2014, 66 (05) :851-860
[4]   Uncovering the role of 5-hydroxymethylcytosine in the epigenome [J].
Branco, Miguel R. ;
Ficz, Gabriella ;
Reik, Wolf .
NATURE REVIEWS GENETICS, 2012, 13 (01) :7-13
[5]   Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome? [J].
Brothman, AR ;
Swanson, G ;
Maxwell, TM ;
Cui, J ;
Murphy, KJ ;
Herrick, J ;
Speights, VO ;
Isaac, J ;
Rohr, LR .
CANCER GENETICS AND CYTOGENETICS, 2005, 156 (01) :31-36
[6]   Loss of 5-hydroxymethylcytosine is linked to gene body hypermethylation in kidney cancer [J].
Chen, Ke ;
Zhang, Jing ;
Guo, Zhongqiang ;
Ma, Qin ;
Xu, Zhengzheng ;
Zhou, Yuanyuan ;
Xu, Ziying ;
Li, Zhongwu ;
Liu, Yiqiang ;
Ye, Xiongjun ;
Li, Xuesong ;
Yuan, Bifeng ;
Ke, Yuwen ;
He, Chuan ;
Zhou, Liqun ;
Liu, Jiang ;
Ci, Weimin .
CELL RESEARCH, 2016, 26 (01) :103-118
[7]   Epigenetic biomarkers in prostate cancer: Current and future uses [J].
Chiam, Karen ;
Ricciardelli, Carmela ;
Bianco-Miotto, Tina .
CANCER LETTERS, 2014, 342 (02) :248-256
[8]   The CAPRA-S Score A Straightforward Tool for Improved Prediction of Outcomes After Radical Prostatectomy [J].
Cooperberg, Matthew R. ;
Hilton, Joan F. ;
Carroll, Peter R. .
CANCER, 2011, 117 (22) :5039-5046
[9]   The University of California, San Francisco cancer of the prostate risk assessment score: A straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy [J].
Cooperberg, MR ;
Pasta, DJ ;
Elkin, EP ;
Litwin, MS ;
Latini, DM ;
DuChane, J ;
Carroll, PR .
JOURNAL OF UROLOGY, 2005, 173 (06) :1938-1942
[10]   Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer [J].
D'Amico, AV ;
Whittington, R ;
Malkowicz, SB ;
Schultz, D ;
Blank, K ;
Broderick, GA ;
Tomaszewski, JE ;
Renshaw, AA ;
Kaplan, I ;
Beard, CJ ;
Wein, A .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1998, 280 (11) :969-974