Aberrant promoter methylation of the PAQR3 gene is associated with prostate cancer

e16046 Background: The current screening method for prostate cancer (PC), which is based on prostate specific antigen (PSA) level lacks specificity and sensitivity. Previous studies have reported that increased levels of free circulating DNA (fcDNA) and hypermethylation of genes are associated with several cancers. In this study we evaluated the use of fcDNA level and aberrant promoter methylation of 4 genes in serum as biomarkers for PC. Methods: 89 PC patients, 59 with prostatitis (PT) and 104 with benign prostatic hyperplasia (BPH) were enrolled. Serum DNA was analyzed for methylation of GSTPi, RARB, RASSF1A and ECAD by methylation-specific PCR. FcDNA level was analyzed by quantitative PCR. We examined the effect of methylation and fcDNA on PC risk by fitting two logistic regression models, one comparing PC vs BPH and PT vs BPH and the other comparing PC vs PT+BPH. Models were adjusted for age, race, and log2PSA, and tested for variation in effect of methylation by race. Similar analyses assessed the effect of fcDNA as continuous variable, after log2 transformation, and as dichotomous variable with cutpoint near the upper quartile for BPH controls. Results: When adjusted for age and log2PSA, positive GSTPi methylation was associated with increased risk of PC in whites (OR = 6.11, p < 0.001, PC vs BPH; OR = 3.93, p = 0.001, PC vs BPH + PT). Methylation of RARB was associated with PT independent of race (OR = 2.85, p = 0.032, PT vs BPH). Patients with fcDNA ≥180ng/ml were at twice the risk of PC compared to those with levels <180ng/ml, and this result did not vary by race. Models including both GSTPi and fcDNA confirmed the independent effect of these two factors in whites (high fcDNA OR = 3.77, p = 0.002, positive GSTPi methylation OR = 5.41, p < 0.001, PC v. BPH + PT). Although high fcDNA also increased risk of PC in blacks, the effect was not statistically significant (OR = 1.91, p = 0.189, PC vs BPH + PT). Conclusions: Our results suggest that aberrant promoter methylation of GSTPi in serum is a potential biomarker for prostate cancer in whites. Level of fcDNA in serum also appears to be an independent diagnostic marker in whites. No significant financial relationships to disclose.

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Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer

Medical Science Monitor ◽

10.12659/msm.904366 ◽

2017 ◽

Vol 23 ◽

pp. 4895-4900 ◽

Cited By ~ 3

Author(s):

Ying-Li Lin ◽

Yan-Li Li ◽

Jian-Guo Ma

Keyword(s):

Prostate Cancer ◽

Prognostic Marker ◽

Gleason Score ◽

Promoter Methylation ◽

Aberrant Promoter Methylation

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Downregulation of miR-130b~301b cluster is mediated by aberrant promoter methylation and impairs cellular senescence in prostate cancer

Journal of Hematology & Oncology ◽

10.1186/s13045-017-0415-1 ◽

2017 ◽

Vol 10 (1) ◽

Cited By ~ 28

Author(s):

João Ramalho-Carvalho ◽

Inês Graça ◽

Antonio Gomez ◽

Jorge Oliveira ◽

Rui Henrique ◽

...

Keyword(s):

Prostate Cancer ◽

Cellular Senescence ◽

Promoter Methylation ◽

Aberrant Promoter Methylation

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Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is Specific to Prostate Cancer and Predicts Biochemical Disease Recurrence

International Journal of Molecular Sciences ◽

10.3390/ijms22116091 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6091

Author(s):

Kristina Daniunaite ◽

Arnas Bakavicius ◽

Kristina Zukauskaite ◽

Ieva Rauluseviciute ◽

Juozas Rimantas Lazutka ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Practice ◽

Promoter Methylation ◽

Disease Recurrence ◽

The Cancer Genome Atlas ◽

Cancer Dataset ◽

Protein Coding ◽

Diagnosis And Prognosis ◽

Genome Wide ◽

Cancer Genome Atlas

The molecular diversity of prostate cancer (PCa) has been demonstrated by recent genome-wide studies, proposing a significant number of different molecular markers. However, only a few of them have been transferred into clinical practice so far. The present study aimed to identify and validate novel DNA methylation biomarkers for PCa diagnosis and prognosis. Microarray-based methylome data of well-characterized cancerous and noncancerous prostate tissue (NPT) pairs was used for the initial screening. Ten protein-coding genes were selected for validation in a set of 151 PCa, 51 NPT, as well as 17 benign prostatic hyperplasia samples. The Prostate Cancer Dataset (PRAD) of The Cancer Genome Atlas (TCGA) was utilized for independent validation of our findings. Methylation frequencies of ADAMTS12, CCDC181, FILIP1L, NAALAD2, PRKCB, and ZMIZ1 were up to 91% in our study. PCa specific methylation of ADAMTS12, CCDC181, NAALAD2, and PRKCB was demonstrated by qualitative and quantitative means (all p < 0.05). In agreement with PRAD, promoter methylation of these four genes was associated with the transcript down-regulation in the Lithuanian cohort (all p < 0.05). Methylation of ADAMTS12, NAALAD2, and PRKCB was independently predictive for biochemical disease recurrence, while NAALAD2 and PRKCB increased the prognostic power of multivariate models (all p < 0.01). The present study identified methylation of ADAMTS12, NAALAD2, and PRKCB as novel diagnostic and prognostic PCa biomarkers that might guide treatment decisions in clinical practice.

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