scholarly journals GSTP1, APC and RASSF1 gene methylation in prostate cancer samples: comparative analysis of MS-HRM method and Infinium HumanMethylation450 BeadChip beadchiparray diagnostic value

2016 ◽  
Vol 62 (6) ◽  
pp. 708-714 ◽  
Author(s):  
L.O. Skorodumova ◽  
K.A. Babalyan ◽  
R. Sultanov ◽  
A.O. Vasiliev ◽  
A.V. Govorov ◽  
...  

There is a clear need in molecular markers for prostate cancer (PC) risk stratification. Alteration of DNA methylation is one of processes that occur during ÐÑ progression. Methylation-sensitive PCR with high resolution melting curve analysis (MS-HRM) can be used for gene methylation analysis in routine laboratory practice. This method requires very small amounts of DNA for analysis. Numerous results have been accumulated on DNA methylation in PC samples analyzed by the Infinium HumanMethylation450 BeadChip (HM450). However, the consistency of MS-HRM results with chip hybridization results has not been examined yet. The aim of this study was to assess the consistency of results of GSTP1, APC and RASSF1 gene methylation analysis in ÐÑ biopsy samples obtained by MS-HRM and chip hybridization. The methylation levels of each gene determined by MS-HRM were statistically different in the group of PC tissue samples and the samples without signs of tumor growth. Chip hybridization data analysis confirmed the results obtained with the MS-HRM. Differences in methylation levels between tumor tissue and histologically intact tissue of each sample determined by MS-HRM and chip hybridization, were consistent with each other. Thus, we showed that the assessment of GSTP1, APC and RASSF1 gene methylation analysis using MS-HRM is suitable for the design of laboratory assays that will differentiate the PC tissue from the tissue without signs of tumor growth.

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Maibritt Nørgaard ◽  
Christa Haldrup ◽  
Marianne Trier Bjerre ◽  
Søren Høyer ◽  
Benedicte Ulhøi ◽  
...  

Abstract Background Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, resulting in overdiagnosis and overtreatment of clinically insignificant tumors. Thus, to improve the management of PC, novel biomarkers are urgently needed. Results In this study, we integrated genome-wide methylome (Illumina 450K DNA methylation array (450K)) and RNA sequencing (RNAseq) data performed in a discovery set of 27 PC and 15 adjacent normal (AN) prostate tissue samples to identify candidate driver genes involved in PC development and/or progression. We found significant enrichment for homeobox genes among the most aberrantly methylated and transcriptionally dysregulated genes in PC. Specifically, homeobox gene MEIS2 (Myeloid Ecotropic viral Insertion Site 2) was significantly hypermethylated (p < 0.0001, Mann-Whitney test) and transcriptionally downregulated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue in our discovery sample set, which was also confirmed in an independent validation set including > 500 PC and AN tissue samples in total (TCGA cohort analyzed by 450K and RNAseq). Furthermore, in three independent radical prostatectomy (RP) cohorts (n > 700 patients in total), low MEIS2 transcriptional expression was significantly associated with poor biochemical recurrence (BCR) free survival (p = 0.0084, 0.0001, and 0.0191, respectively; log-rank test). Next, we analyzed another RP cohort consisting of > 200 PC, AN, and benign prostatic hyperplasia (BPH) samples by quantitative methylation-specific PCR (qMSP) and found that MEIS2 was significantly hypermethylated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue samples (AN and BPH) with an AUC > 0.84. Moreover, in this cohort, aberrant MEIS2 hypermethylation was significantly associated with post-operative BCR (p = 0.0068, log-rank test), which was subsequently confirmed (p = 0.0067; log-rank test) in the independent TCGA validation cohort (497 RP patients; 450K data). Conclusions To the best of our knowledge, this is the first study to investigate, demonstrate, and independently validate a prognostic biomarker potential for MEIS2 at the transcriptional expression level and at the DNA methylation level in PC.


Epigenetics ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. 1037-1045 ◽  
Author(s):  
Ekaterina Olkhov-Mitsel ◽  
Theodorus van der Kwast ◽  
Ken Kron ◽  
Hilmi Ozcelik ◽  
Laurent Briollais ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (35) ◽  
pp. 58199-58209 ◽  
Author(s):  
Yuanyuan Tang ◽  
Shusuan Jiang ◽  
Yinmin Gu ◽  
Weidong Li ◽  
Zengnan Mo ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0133836 ◽  
Author(s):  
Árpád V. Patai ◽  
Gábor Valcz ◽  
Péter Hollósi ◽  
Alexandra Kalmár ◽  
Bálint Péterfia ◽  
...  

2005 ◽  
Vol 44 (04) ◽  
pp. 516-519 ◽  
Author(s):  
H. M. Müller ◽  
H. Fiegl ◽  
M. Widschwendter ◽  
G. Goebel

Summary Objectives: Changes in the status of DNA methylation, known as epigenetic alterations, are among the most common molecular alterations in human neoplasia. For the first time, we reported on the analysis of fecal DNA from patients with CRC to determine the feasibility, sensitivity and specificity of this approach. We want to present basic information about DNA methylation analysis in the context of bioinformatics, the study design and several statistical experiences with gene methylation data. Additionally we outline chances and new research questions in the field of DNA methylation. Methods: We present current approaches to DNA methylation analysis based on one reference study. Its study design and the statistical analysis is reflected in the context of biomarker development. Finally we outline perspectives and research questions for statisticians and bioinformaticians. Results: Identification of at least three genes as potential DNA methylation-based tumor marker genes (SFRP2, SFRP5, PGR). Conclusions: DNA methylation analysis is a rising topic in molecular genetics. Gene methylation will push the extension of biobanks to include new types of genetic data. Study design and statistical methods for the detection of methylation biomarkers must be improved. For the purpose of establishing methylation analysis as a new diagnostic/prognostic tool the adaptation of several approaches has become a challenging field of research activity.


2020 ◽  
Author(s):  
Suk Ling Ma ◽  
Nelson Leung Sang Tang ◽  
Linda Chiu Wa Lam

Background: Pin1 is a propyl cis-trans isomerase and it has been associated with age-at-onset of Alzheimer's disease (AD) and other pathological characteristic of AD. DNA methylation is one of the gene regulation and it might affect the gene expression. Objectives: This study was aimed to examine the correlation between DNA methylation and gene expression of Pin1 and its effect on the risk of AD in a Chinese population. Methods: 80 AD patients and 180 normal controls were recruited in this study and their cognitive function were assessed. Pin1 gene expression and methylation were quantified by real-time RT-PCR and Melting Curve Analysis-Methylation assay (MCA-Meth) respectively. Results: Our finding revealed a positive correlation between methylation and gene expression of Pin1 (p=0.001) and increased Pin1 methylation was predisposed to the risk of AD (p<0.001). CG genotype of Pin1 SNP rs2287839 was associated with higher gene expression of Pin1 (p=0.036) and the effect was only prominent in normal controls as AD patients were already methylated at Pin1 promoter. Furthermore, methylation of Pin1 was associated with better performance in cognition (p=0.018). Conclusions: Our result further supported the involvement of Pin1 in AD and the increased level of Pin1 might be a protective factor for AD.


Sign in / Sign up

Export Citation Format

Share Document