The association of retinoic acid receptor beta2(RARβ2) methylation status and prostate cancer risk: a systematic review and meta-analysis.

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

The association of RAS association domain family Protein1A (RASSF1A) methylation states and bladder cancer risk: a systematic review and meta-analysis.

RAS association domain family protein 1a (RASSF1A) is a putative tumor suppressor gene located on 3p21, has been regarded playing important roles in the regulation of different types of human tumors. Previous reports demonstrated that the frequency of RASSF1A methylation was significantly higher in patients group compared with controls, but the relationship between RASSF1A promoter methylation and pathological features or the tumor grade of bladder cancer remains controversial. Therefore, A meta-analysis of published studies investigating the effects of RASSF1A methylation status in bladder cancer occurrence and association with both pTNM (p, pathologic stage; T, tumor size; N, node status; M, metastatic status) and tumor grade in bladder cancer was performed in the study. A total of 10 eligible studies involving 543 cases and 217 controls were included in the pooled analyses. Under the fixed-effects model, the OR of RASSF1A methylation in bladder cancer patients, compared to non-cancer controls, was 8. 40 with 95%CI=4. 96-14. 23. The pooled OR with the random-effects model of pTNM and tumor grade in RASSF1A methylated patients, compared to unmethylated patients, was 0. 75 (95%CI=0. 28-1. 99) and 0. 39 (95%CI=0. 14-1. 09). This study showed that RASSF1A methylation appears to be an independent prognostic factor for bladder cancer. The present findings also require confirmation through adequately designed prospective studies

Begg's funnel plot with pseudo 95% confidence limits of publication bias test for association between RAR beta2 methylation and pathological state.

<p>Begg's funnel plot with pseudo 95% confidence limits of publication bias test for association between RAR beta2 methylation and pathological state.</p

Stratified analyses of RARβ2 methylation and prostate cancer risk.

a<p>Number of comparisons.</p>b<p>Between group heterogeneity not calculated; only valid with inverse variance method.</p

Main results of eligible studies evaluating RARβ2 methylation and pathologic stage/Gleason score in prostate cancer.

a<p>Number of comparisons.</p>b<p>Between group heterogeneity not calculated; only valid with inverse variance method.</p

Begg's funnel plot with pseudo 95% confidence limits of publication bias test for RASSF1A methylation.

<p>Each point represented a separate study for the indicated association. Logor natural logarithm of OR, horizontal line mean effect size. A: Begg's funnel plot of publication bias test. B: Begg's funnel plot of publication bias test after trim-and-fill method.</p

Begg's funnel plot with pseudo 95% confidence limits of publication bias test for association between RAR beta2 methylation and Gleason score.

<p>Begg's funnel plot with pseudo 95% confidence limits of publication bias test for association between RAR beta2 methylation and Gleason score.</p

Characteristics of studies included in this meta-analysis.

<p>MSP, methylati on specific PCR; QMSP, quantitative methylation specific PCR. ^aP pathologic stage; ^bRARβ2 methylated/RARβ2 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.</p

Main results of eligible studies evaluating RASSF1A methylation and pTNM/grade in bladder cancer.

a<p>Number of comparisons.</p

Begg's funnel plot with pseudo 95% confidence limits of publication bias test for RASSF1A methylation.

<p>Each point represented a separate study for the indicated association. Logor natural logarithm of OR, horizontal line mean effect size. Fig. 1: Begg’s funnel plot of publication bias test.</p