Abstract
Prostate cancer (PCa) remains as one of the most common cause of cancer related death among men in the US. The widely used prostate specific antigen (PSA) screening is limited by low specificity. The diagnostic value of other biomarkers such as RAS association domain family protein 1 A (RASSF1A) promoter methylation in prostate cancer and the relationship between RASSF1A methylation and pathological features or tumor stage remains to be established. Therefore, a meta-analysis of published studies was performed to understand the association between RASSF1A methylation and prostate cancer. In total, 16 studies involving 1431 cases and 565 controls were pooled with a random effect model in this investigation. The odds ratio (OR) of RASSF1A methylation in PCa case, compared to controls, was 14.73 with 95% CI = 7.58–28.61. Stratified analyses consistently showed a similar risk across different sample types and, methylation detection methods. In addition, RASSF1A methylation was associated with high Gleason score OR=2.35, 95% CI: 1.56–3.53. Furthermore, the pooled specificity for all included studies was 0.87 (95% CI: 0.72–0.94), and the pooled sensitivity was 0.76 (95% CI: 0.55–0.89). The specificity in each subgroup stratified by sample type remained above 0.84 and the sensitivity also remained above 0.60. These results suggested that RASSF1A promoter methylation would be a potential biomarker in PCa diagnosis and therapy.
Highlights
Prostate cancer remains as one of the most common cause of cancer related death among men in the US, with an estimated 29,720 deaths projected in 2013 [1,2]
Inclusion and Exclusion Criteria Studies were selected for analysis if they met the following criteria(1): measurement of DNA methylation in one of the following samples: blood, plasma, serum, urine or prostate tissues; (2) the subjects in every study comprised of prostate cancer patients and non-cancer controls; (3) Data was included in the analysis only if the full text of the article was in English
All cases were from biopsy confirmed Prostate cancer (PCa) or high grade prostatic intra-epithelial neoplasia (HGPIN), while controls were limited to either benign prostatic hyperplasia (BPH), healthy subjects or those who had genitourinary cancer with a healthy prostate
Summary
Prostate cancer remains as one of the most common cause of cancer related death among men in the US, with an estimated 29,720 deaths projected in 2013 [1,2]. With a sensitivity of 80%, PSA screening significantly increases the early diagnosis of prostate cancer, the PSA screening has only 20% specificity, which may lead to unnecessary biopsies and overtreatment [4]. Aberrant DNA methylation of gene promoters is characteristic of cancer cells, and several genes are epigenetically altered in a cancer specific manner. GSTP1 gene promoter methylation is widely characterized by several independent groups and is found to be have diagnostic value in prostate cancer [6,7]. More than one hundred genes are reported as methylation targets in prostate cancer, which may represent a promising method for monitoring the occurrence and progression of cancer [7,8,9]. Hypermethylation of the CpG islands within the RASSF1A promoter region are the Author
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