Association between DNA methylation of HSPB1 and death in low Gleason score prostate cancer

Vasiljević, Nataša; Ahmad, Amar; Beesley, Carol; Thorat, Mangesh A.; Fisher, Gabrielle; Berney, Daniel M.; Møller, Henrik; Ye, Yu; Lu, Yong‐Jie; Cuzick, Jack; Foster, Christopher S.; Lörincz, Attila T.

doi:10.1038/pcan.2012.47

Cited by 33 publications

(23 citation statements)

References 27 publications

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“…These studies have identified new potential tumor markers including methylation of PITX2 , HOXD3 , APC , TGFβ2 , RASSF1A , ANEP , PCDH10 , ZNF132 , TDRD1 , AOX1 , C1orf114 , GAS6 , HAPLN3 , KLF8 , MOB3B , CCND2 , PTGS2 , RARB , SRD5A2 and CYP11A1 , thus emerging as new predictors of BCR particularly in high-risk clinically localized disease. Also the level of methylation of HSPB1 , the gene encoding heat shock protein-27 [25], and Ras association (RalGDS/AF-6) domain family member 1 ( RASSF1 ) [26] associate to death in low Gleason score PCa.…”

Section: Discussionmentioning

confidence: 99%

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Angulo

López

Dorado³

et al. 2016

Urol Int

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Purpose: Detection of DNA hypermethylation is emerging as a novel molecular biomarker for different malignancies. We intend to define whether a hypermethylation profile of patients with prostate cancer (PCa) predicts biochemical recurrence (BCR) after radical prostatectomy (RP). Material and Methods: Genome-wide methylation analysis was performed using the GoldenGate Methylation Cancer Panel-I (Illumina, Inc.) on 10 normal prostate tissues and 58 tumor samples from patients treated by RP followed for prostate-specific antigen (PSA) failure (>0.4 ng/ml) and disease progression. Patients were classified on the basis of D'Amico criteria according to clinical staging, PSA at diagnosis and Gleason score after pathologist review. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Hierarchical clustering analysis was performed and relationships with outcome were investigated using log-rank analysis and Cox regression model. Results: We found 28 genes significantly hypermethylated in >20% of the tumors analyzed. Four clusters of patients were characterized by their DNA methylation profile, one at higher risk to develop BCR (p = 0.005). Multivariate analysis revealed patients in this cluster (HR 2.56), and high-risk patients (HR 4.34) according to D'Amico classification were independent predictors of BCR after prostatectomy. From the selected genes MT1A, ALOX12, GSTM2, APC, MYCL2 and RARB hypermethylation predicted BCR and GSTM2 (HR 3.78) and MYCL2 hypermethylation (HR 2.71) did so independently. Conclusion: Epigenetic silencing of GSTM2 and MYCL2 comprise novel molecular markers to predict BCR after surgery for medium- and high-risk localized PCa undergoing surgical treatment and hypermethylation of these genes could be incorporated to the clinical and pathological factors defining the patient at higher risk of PSA failure after prostatectomy. The limitation of the study is that no independent validation cohort is analysed.

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Section: Discussionmentioning

confidence: 99%

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

Angulo

López

Dorado³

et al. 2016

Urol Int

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“…A majority of the studies focusing on the prognostic value of methylation have used time to biochemical recurrence after surgical treatment as the primary surrogate end point, which does not accurately estimate the potential of the cancer in terms of risk of death if left untreated. We recently reported the prognostic value of methylation of HSPB1 to predict men at risk of dying from PCa in a watchful waiting cohort [15]. In the current casecontrol study, we used the same cohort but focused on patients with localized PCa of Gleason score ≤7 and investigated if methylation of additional genes can predict poor survival.…”

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confidence: 98%

“…A growing body of evidence indicates that methylation has potential to improve the sensitivity for PCa diagnosis [14]. In addition, it has been suggested that DNA methylation assays could be prognostic and complementary or perhaps an alternative to other prognostic tests such as the CCP score, immunohistochemisty or other kinds of approaches [9,15,16]. Methylation assays have desirable features such as robust measurement of stable DNA and the potential of inexpensive assays [17] tools for predicting aggressive PCa [18].…”

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confidence: 99%

DNA Methylation of PITX2 Predicts Poor Survival in Men with Prostate Cancer

et al. 2014

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“…DNA methylation is a mitotically transmitted epigenetic motif that can be measured with good accuracy in tissue biopsies, exfoliated cells, blood and other fluids and can be related to exact physical locations in the genome; this feature lends itself more readily to medical diagnostics. Clinically relevant methylation changes are known in many human cancers such as cervix, prostate, breast, colon, bladder, stomach, oesophagus and lung cancers [1,[10][11][12] . Differential methylation may have a central role in the development and outcome of most if not all human malignancies.…”

Section: The Interface Of Epigenetics and Geneticsmentioning

confidence: 99%

Virtues and Weaknesses of DNA Methylation as a Test for Cervical Cancer Prevention

Lörincz¹

2016

Acta Cytologica

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in cervical tissue, close to 20 have been reported in different studies, and approximately 10 have been repeatedly shown to have elevated methylation in cervical cancers and highgrade CIN (CIN2 and CIN3), most prominently CADM1, EPB41L3, FAM19A4, MAL, PAX1 and SOX1. Obtaining consistent performance data from the literature is quite difficult because most methylation studies used a variety of different assay methodologies and had incomplete and/or biased clinical specimen sets, varying assay thresholds and disparate target gene regions. There have been relatively few validation studies of DNA methylation biomarkers in large population-based screening studies, but an encouraging development more recently is the execution of well-designed studies to test the true performance of the markers in real-world settings. Methylation of HPV genes, especially HPV16, HPV18, HPV31, HPV33 and HPV45, in disease progression has been a major focus of research. Elevated methylation of the HPV16 L1 and L2 open reading frames, in particular, is associated with CIN2, CIN3 and invasive cancer. Essentially all cancers have high levels of methylation for human genes and for driver HPV types, which suggests that quantitative methylation tests may have utility in predicting CIN2 and CIN3 that are likely to progress. It is still early in the process of development of methylation biomarkers, but already they are showing strong promise as a universal and systematic approach to molecular triage, applicable to all Key WordsEpigenetics · DNA methylation · Cervical intraepithelial neoplasia · Cervical cancer · Human papillomavirus · Biomarkers · Triage · Diagnostics · Molecular signature · Classifier · Score Abstract Epigenetics is the study of heritable and non-heritable genetic coding that is additive to information contained within classical DNA base pair sequences. Differential methylation has a fundamental role in the development and outcome of malignancies, chronic and degenerative diseases and aging. DNA methylation can be measured accurately and easily via various molecular methods and has become a key technology for research and healthcare delivery, with immediate roles in the elucidation of disease natural history, diagnostics and drug discovery. This review focuses on cancers of the lower genital tract, for which the most epigenetic information exists. DNA methylation has been proposed as a triage for women infected with human papillomavirus (HPV) and may eventually directly complement or replace HPV screening as a one-step molecular diagnostic and prognostic test. Methylation of human genes is strongly associated with cervical intraepithelial neoplasia (CIN) and cancer. Of the more than 100 human methylation biomarker genes tested so far

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Association between DNA methylation of HSPB1 and death in low Gleason score prostate cancer

Cited by 33 publications

References 27 publications

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

A DNA Hypermethylation Profile Independently Predicts Biochemical Recurrence Following Radical Prostatectomy

DNA Methylation of PITX2 Predicts Poor Survival in Men with Prostate Cancer

Virtues and Weaknesses of DNA Methylation as a Test for Cervical Cancer Prevention

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