Combined Hypermethylation of APC and GSTP1 as a Molecular Marker for Prostate Cancer: Quantitative Pyrosequencing Analysis

Abstract

A total of 149 human prostate tissues obtained from our institute were assessed: 52 specimens of benign prostate hyperplasia (BPH) and 97 specimens of prostate cancer (PCa). The methylation status of the genes of Adenomatous polyposis coli (APC) and glutathione-S-transferase-P1 (GSTP1) was analyzed by quantitative pyrosequencing. A methylation score (M score) was calculated to capture the combined methylation level of both genes. The methylation level of each single gene and that of both genes combined was significantly higher in PCa specimens than in BPH (each p < 0.001). The value of APC methylation, GSTP1 methylation, and M score for predicting PCa was measured by the area under the receiver operating characteristic (ROC) curve and reached 0.954, 0.942, and 0.983, respectively. The sensitivity and specificity of the M score in discriminating between PCa and BPH reached 92.8% and 100.0%, respectively. The M score was positively associated with the serum prostate-specific antigen (PSA) level (p trend < 0.001). Our study demonstrates that the quantitative measurement of two methylation markers might drastically improve the ability to discriminate PCa from BPH.

Olfactomedin 4 downregulation is associated with tumor initiation, growth and progression in human prostate cancer

“…DNA methylation is abnormally regulated in many cancer types, including prostate cancer . We found here that increased CpG site methylation in the OLFM4 gene promoter region was associated with reduced expression of OLFM4 , which is similar to what has been observed for tumor‐suppressor genes (e.g., APC , RASSF1A and GSTP1 ) during the progression of prostate cancer . Importantly, we have identified three CpG sites (−681, −446 and −91) that were increased methylation in the high‐grade prostate cancer tissues examined.…”

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

“…Our search strategy and application of the inclusion/exclusion criteria resulted in a total of 19 articles that were included in the systematic review. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] A description of the included studies is given in Tables 1 and 2. The following data were recorded for each study: author's name, year of publication, sample forms, method, 5 0 -3 0 primers (forward and reverse, respectively), amplicon size (bp) and annealing temperature (1C), country, race, cancer clinical classification, PSA, Gleason score, type of cases and controls, type of PCR method and other relevant characteristics of the study population.…”

“…[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] Finally, 19 studies met the inclusion criteria and were included. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Among these 19 studies, 5 involved body fluid (blood, urine and so on) [11][12][13][14][15] and the remaining 14 articles involved sample tissues. [16][17][18][19][20][21][22][23][24][25][26][27]…”

“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Among these 19 studies, 5 involved body fluid (blood, urine and so on) [11][12][13][14][15] and the remaining 14 articles involved sample tissues. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] Ten studies used quantitative real-time methylation-specific PCR (QMSP) to detect APC methylation, 11,13,14,18,19,[21][22][23]25,26 seven were conducted using the method of methylation-specific PCR (MSP), 12,15,...…”

“…[16][17][18][19][20][21][22][23][24][25][26][27][28][29] Ten studies used quantitative real-time methylation-specific PCR (QMSP) to detect APC methylation, 11,13,14,18,19,[21][22][23]25,26 seven were conducted using the method of methylation-specific PCR (MSP), 12,15,17,20,24,27,29 and two studies used pyrosequencing. 16 Specificity and sensitivity of APC promoter methylation using different types of samples All the results are shown in Table 3. The pooled specificity for all included studies was 0.91 (95% CI: 0.82-0.95), and the pooled sensitivity was 0.78 (95% CI: 0.63-0.88).…”