DNA Methylation Changes Correlate with Gleason Score and Tumor Stage in Prostate Cancer

Delgado‐Cruzata, Lissette; Hruby, Gregory W.; González, Karina; McKiernan, James M.; Benson, M. C.; Santella, Regina M.; Shen, Jing

doi:10.1089/dna.2011.1311

Cited by 38 publications

(30 citation statements)

References 47 publications

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“…On the other hand, there was no association between LINE-1 methylation and Gleason score. Although this latter finding is not completely inconsistent with previous studies (a clear association between LINE-1 hypomethylation and Gleason score has been found only in one out of 3 previous studies 22,23,26 ), if global methylation was a late event in prostate cancerogenesis, we would have expected higher hypomethylation among patients with a Gleason score of at least 8. It could be speculated that global methylation is more related to the metastatic potential of aggressive prostate cancers than to the Gleason score, and it is of interest that previous studies strongly indicate a decreased global methylation in the prostate cancer tissue among prostate cancer patients with systemic metastases.…”

Section: Discussioncontrasting

confidence: 75%

“…We have recently conducted a systematic review of studies on prostatic tumor global hypomethylation and prostate cancer progression: 19 although studies were heterogeneous and mostly based on a limited sample size, global hypomethylation was reported to be associated with high Gleason score, advanced tumor stage, high pre-operative PSA, and presence of metastasis. [20][21][22][23][24][25][26] The genome-wide methylation level of the long interspersed nuclear element-1 (LINE-1) is considered as a good surrogate marker for global methylation, [27][28][29] as LINE-1 is widely interspersed and represents about 15% of human genome. 30,31 Thus, in the present study we have analyzed prostate tissue LINE-1 methylation status in a cohort of prostate cancer patients in association with Gleason score, gene-specific hypermethylation, and mortality from prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

et al. 2016

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Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.Abbreviations: NTAT, non-neoplastic tissue adjacent to tumor; LINE-1, long interspersed nuclear element-1; PIN, prostatic intraepithelial neoplasia; APC, adenomatous polyposis coli; GSTP1, glutathione S-transferase 1; TURP, transurethral resection of the prostate; HR, hazard ratio; CI, confidence interval; MAR, missing at random

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Section: Discussioncontrasting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

et al. 2016

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“…[7][8][9][10][11] However, relatively limited studies have used the quantitative PSQ method to explore DNA hypermethylation status of various genes in PCa. 5,6 In the earlier studies using multiple genes by the PSQ method, it was demonstrated that both APC and GSTP1 methylation levels were significantly higher in PCa samples than in control samples. 5,6 Our study confirmed the study method and results of previous quantitative analysis.…”

Section: Figure 1 Methylation Level Of (A) Adenomatous Polyposis Colmentioning

confidence: 99%

“…4,5 It is a sensitive and highly reproducible method that is uniquely suited to the analysis of clinical specimens from which only small amounts of DNA can be isolated. 5,6 Adenomatous polyposis coli (APC) and glutathione-Stransferase-P1 (GSTP1) are well-characterized tumor suppressor genes. Methylation of these genes is associated with PCa.…”

Section: Introductionmentioning

confidence: 99%

“…Methylation of these genes is associated with PCa. [5][6][7][8][9][10][11][12] Although a single molecular marker may be promising, the reliance on a single gene for the screening and diagnosis of PCa presents some limitations. [10][11][12] These limitations could potentially be overcome by the simultaneous use of multiple sensitive and specific molecular markers.…”

Section: Introductionmentioning

confidence: 99%

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

Yoon

Kim

et al. 2012

SLAS Discovery

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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.

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A six‐CpG‐based methylation markers for the diagnosis of ovarian cancer in blood

Wang

et al. 2019

J of Cellular Biochemistry

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DNA methylation markers in the peripheral blood are able to be applied to treat epithelial cancer. Nevertheless, the diagnostic potential value of it for ovarian cancer (OV) has not been studied. The study aimed to explore the difference of DNA methylation in peripheral blood between OV patients and healthy women. Firstly, the whole blood of DNA methylation data was provided by the Gene Expression Omnibus (GEO) database. The linear model was applied to the identification of significantly differentially expressed methylated CpG sites (differentially methylation sites [DMP]), and the further screen of co‐expression CpG sites (Co‐DMP). A total of 2812 DMPs were identified, and weighted gene co‐expression network analysis helped to obtain seven co‐expression modules. Among them, the yellow module was the most related to OV. Co‐DMPs (167) in the yellow module were mainly distributed near the transcription start sites. However, most of them were not in the CpG island. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to the identification of stable OV‐related blood biomarkers that six Co‐DMPs (cg00134539, cg00226923, cg25268718, cg25697314, cg25839227, cg26574610) with the highest frequency were found as potential biomarkers. Finally, the diagnostic classifier was established using the support vector machine (SVM) with the accuracy rate of 87.1% and 74.5% in training data set and validation data set, respectively. To sum up, a new feature was provided here for the diagnosis of OV, which is helpful for the diagnosis and individualized treatments of early OV.

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DNA Methylation Changes Correlate with Gleason Score and Tumor Stage in Prostate Cancer

Cited by 38 publications

References 47 publications

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

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

A six‐CpG‐based methylation markers for the diagnosis of ovarian cancer in blood

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