Abstract
The retinoic acid receptor beta2(RARβ2) is a type of nuclear receptor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, which has been shown to function as a tumor suppressor gene in different types of human tumors. Previous reports demonstrated that the frequency of RARβ2 methylation was significantly higher in prostate cancer patients compared with controls, but the relationship between RARβ2 promoter methylation and pathological stage or Gleason score of prostate cancer remained controversial. Therefore, a meta-analysis of published studies investigating the effects of RARβ2 methylation status in prostate cancer occurrence and association with both pathological stage and Gleason score in prostate cancer was performed in the study. A total of 12 eligible studies involving 777 cases and 404 controls were included in the pooled analyses. Under the random-effects model, the pooled OR of RARβ2 methylation in prostate cancer patients, compared to non-cancer controls, was 17.62 with 95%CI = 6.30–49.28. The pooled OR with the fixed-effects model of pathological stage in RASSF1A methylated patients, compared to unmethylated patients, was 0.67 (95%CI = 0.40–1.09) and the pooled OR of low-GS in RARβ2 methylated patients by the random-effect model, compared to high-GS RARβ2 methylated patients, was 0.54 (95%CI = 0.28–1.04). This study showed that RARβ2 might be a potential biomarker in prostate cancer prevention and diagnosis. The detection of RARβ2 methylation in urine or serum is a potential non-invasive diagnostic tool in prostate cancer. The present findings also require confirmation through adequately designed prospective studies.
Highlights
Prostate cancer is the most commonly diagnosed noncutaneous neoplasia in the world
Inclusion and exclusion criteria Studies were selected for analysis if they met the following criteria: 1) they were original epidemiological studies on the correlation between RARb2 promoter methylation and the prognosis of prostate cancer patients; 2) RARb2 methylation status was examined using methylation-specific PCR (MSP) or quantitative methylation specific PCR (MSP) (QMSP); 3)the subjects in every study comprised patients and non-cancer controls; 3) studies should be with full text abstracts for relevant information extraction; 4) when the same patient population reported in several publications, only the most recent report or the most complete one was included in this analysis to avoid overlapping between cohorts; 5) the numbers of patients and controls in each study should be more than 5 respectively
MSP, methylati on specific PCR; QMSP, quantitative methylation specific PCR. aP pathologic stage; bRARb2 methylated/RARb2 unmethylated; cpathologic stage# T2 was defined as low-stage and pathologic stage$ T3 was defined as high-stage; dGleason score#6 was defined as low-GSand Gleason score$7 was defined as high-GS. doi:10.1371/journal.pone.0062950.t001
Summary
The disease predominantly affects men after the 6th decade of life and is associated with considerable morbidity and mortality [1]. Methylation of CpG islands within the promoter and/ or 59 regions of genes is recognized as a common alteration in cancer-related genes often associated with partial or complete transcriptional disruption [5]. This epigenetic alteration provides an alternative pathway to gene silencing in addition to gene mutation or deletion, which is suggested to be a new molecular marker for early cancer detection [6]. P1 directs the transcription of isoform RARb1, whereas P2 promotes the transcription of isoforms RARb2 and RARb4 [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
