APC gene hypermethylation and prostate cancer: a systematic review and meta-analysis

Abstract

Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is limited. This study analyzes the sensitivity and specificity of adenomatous polyposis coli (APC) methylation for PCa detection in body fluids and tissues. Combining search results from PubMed and Embase, 19 studies were included, 5 involving body fluids and 14 involving prostate tissue, with 2344 subjects. In body fluid subgroups, the pooled sensitivity and specificity was 0.53 (95% confidence interval (CI): 0.28-0.78) and 0.92 (95% CI: 0.86-0.95), respectively. From tissue studies, the results presented as 0.84 (95% CI: 0.70-0.92) and 0.91 (95% CI: 0.77-0.97). To confirm the results, we conducted a further analysis by removing studies which introduced high heterogeneity due to the type of cases and controls. The same degree of sensitivity and specificity was presented in two subgroups (urine: sensitivity 0.46, 95% CI: 0.39-0.53; specificity 0.87, 95% CI: 0.64-0.96; tissue: sensitivity 0.87, 95% CI: 0.72-0.94; specificity 0.89, 95% CI: 0.68-0.97). In addition, analysis of the interaction between APC methylation and PCa showed strong association in the whole data set (odds ratio (OR) ¼ 24.91, 95% CI: 12.86-48.24, I 2 ¼ 72.5%). Pooling the same two main subgroups (tissue/fluid) gave a pooled OR of 33.54 (95% CI: 14.88-75.59; I 2 ¼ 70.7%) and 8.20 (95% CI: 2.84-23.74, I 2 ¼ 64.2%), respectively. From this study, the results suggest that APC promoter methylation may be the potential testing for PCa diagnosis and provide a new viewpoint in the treatment of PCa.

SOX9 drives WNT pathway activation in prostate cancer

“…Interestingly, in adult human prostate, stromal WNT16B was identified as a factor mediating epithelial cell resistance to DNA-damaging agents (67). WNT signaling in advanced PCa may also be enhanced by APC gene methylation or by mutations in key components of the WNT signaling pathway (70)(71)(72). Overall, these findings indicate that WNT synthesis and signaling are driving at least a subset of PCa, in particular those tumors with high SOX9 levels, and that this subset of PCa may be responsive to WNT synthesis inhibitors or other WNT pathway antagonists that are now entering the clinic. )…”

Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records

“…Inappropriate activation of this pathway through loss of APC function contributes to cancer progression, as in familial adenomatous polyposis [29]. Mutations in APC may result in colorectal cancer [30], prostate cancer [31], and other cancers [32]. The BRCA1 gene is a protein product and is responsible for DNA repair [33].…”

DNA Methylation-Mediated Downregulation of DEFB1 in Prostate Cancer Cells

“…Further, methylation of GSTP1 appears to perform better in combination with prostate-specific antigen (PSA) and other methylation biomarkers [7]. Remarkably, the APC gene was frequently found to be methylated in PCa [10], and methylation of the RASSF1a promoter was strongly correlated with an increased risk of PCa aggressiveness and tumor progression [11,12]. Notably, a combination of GSTP1 , RARß2 , RASSF1a , and APC has been the best at discriminating cancer from non-cancer specimens [13].…”