All biopsy cores from the negative index biopsy were profiled for the epigenetic biomarkers GSTP1, APC, and RASSF1 using ConfirmMDx for Prostate Cancer (MDxHealth, Irvine, CA).
But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596-1.2655) or GSTP1A131G polymorphism (OR = 1.0845, 95% CI = 0.96-1.2251) and the PCa risk.
GSTP1 CpG island hypermethylation, a somatic epigenetic alteration, appears poised to serve as a molecular biomarker useful for prostate cancer screening, detection, and diagnosis.
Importantly, the GSTP1 cycle threshold value demonstrated a good correlation (R = 0.84) with the number of cores found to contain prostate cancer or premalignant lesions on biopsy.
Methylation-specific PCR (MSP) methods allowed for the successful detection of GSTP1 methylation in body fluids (serum, plasma, urine, and ejaculates) from prostate cancer patients.
Gene-based biomarkers in urine such as prostate cancer antigen-3 (PCA3), and genes for transmembrane protease serine-2 (TMPRSS2), and glutathione S-transferase P (GSTP1) have been developed and evaluated in the past decades.
Population-based case-control studies have found relationships between risk of prostate cancer and genetic polymorphisms in the CAG repeat and GGC repeat of the X-linked androgen receptor gene (AR) as well as the autosomal gene coding for glutathione S-transferase pi (GSTP1).
The use of real-time quantitative polymerase chain reaction to detect hypermethylation of the CpG islands in the promoter region flanking the GSTP1 gene to diagnose prostate carcinoma.
Human prostate cancer (PCA) cells characteristically contain hypermethylated CpG island sequences encompassing the transcriptional regulatory region of GSTP1, the gene encoding the pi-class glutathione S-transferase (GSTP1), and fail to express GSTP1 as a consequence of transcriptional "silencing."
Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas.
The present study explores the effects of restored GSTP1 expression on glutathione levels, accumulation of oxidative DNA damage, and prostate cancer cell survival following oxidative stress induced by protracted, low dose rate ionizing radiation (LDR).
A potential multiplicative interaction was suggested between GSTP1 and smoking on the risk of prostate cancer with the adjusted OR for the interaction of 4.52 (95% CI: 1.07-19.17).
Despite widely noted heterogeneous nature of PCa, gene expression alterations of AMACR, DD3, and GSTP1 in LCM-derived PCa epithelial cells suggest for common underlying mechanisms in the initiation of PCa.
GSTP1 methylation in the first and in the second negative biopsy was associated with prostate cancer detection [OR per 1% increase: 1.14 (95% CI 1.01-1.29) for the second biopsy and 1.21 (95% CI 1.07-1.37) for the highest methylation level (first or second biopsy)].
We identified five highly methylated genes in prostate cancer: GSTP1, RARB, RASSF1, SCGB3A1, CCND2 (P < 0.0001), with an area under the ROC curve varying between 0.89 (95 % CI 0.82-0.97) and 0.95 (95 % CI 0.90-1.00).