Serum GADD45a methylation is a useful biomarker to distinguish benign vs malignant prostate disease

Abstract

Background:Prostate-specific antigen (PSA) screening for prostate cancer results in a large number of unnecessary prostate biopsies. There is a need for specific molecular markers that can be used in combination with PSA to improve the specificity of PSA screening. We examined GADD45a methylation in blood DNA as a molecular marker for prostate cancer diagnosis.Methods:The study included 82 men, with PSA levels >4 ng ml−1 and/or abnormal digital rectal exam, who underwent prostate biopsy. We compared GADD45a methylation in DNA from serum and buffy coat in 44 patients (22 prostate cancer and 22 benign). GADD45a methylation in serum DNA was examined in 82 patients (34 cancer and 48 benign).Results:There was no significant difference in buffy coat GADD45a methylation between cancer and benign patients. Serum GADD45a methylation was significantly higher in cancer than in benign patients. Classification and regression tree predictive model for prostate cancer including risk groups defined by PSA, free circulating DNA (fcDNA) level and GADD45a methylation yielded specificity of 87.5%, sensitivity of 94.1% and receiver operator characteristic curve area of 0.937.Conclusions:Serum GADD45a methylation in combination with PSA and fcDNA level was useful in distinguishing benign from prostate cancer patients.

DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients

“…They are engaged in regulating of intrinsic apoptotic pathways. Previous studies on different human cancers have analysed and confirmed the DNA methylation changes in these genes, but none of them were demonstrated these changes in EC San Jose-Eneriz et al 2009;Perugini et al 2013;Cho et al 2014;Kucuk et al 2015;Reis et al 2015).…”

“…Overexpression of GADD45A causes dissociation of BIM from the microtubule-associated components and translocation to mitochondria (Tong et al 2005). So far increased DNA methylation level in promoter region of GADD45A gene was observed in breast, prostate cancer and acute myeloid leukemia where it is associated with decreased expression level, poor prognosis a might be useful as marker to distinguish benign vs. malignant solid tumors (Perugini et al 2013;Reis et al 2015). These result are inconsistent with ours, thus we can only suggest that methylation of GADD45A gene can be included in EEC-L development.…”

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

“…GADD45a methylation in prostate cancer plasma is apparently higher than in benign prostate tumor plasma [84]. Other circulating methylation markers include SESN3 [82], WIF1, and NPY [85] for localized colorectal cancer, RAS [86], PTK2, WIF1, and NPY [85] for metastatic colorectal cancer, TAC1 [87] promoter for esophageal adenocarcinoma, RASSF1A [81] for thyroid cancer, SEPT9 [88] for hepatocellular carcinoma, and SHOX2 and SEPT9 [89] for head and neck squamous cell carcinomas.…”

The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention

“…Previous studies have identified an array of genes subjected to methylation-dependent transcriptional silencing in melanoma. Furthermore, detection of methylated genomic DNA in peripheral blood is an attractive potential source of cancer biomarkers because of the stability of DNA and the relative specificity of methylation for malignant disease (14). The requirement for sensitive and specific biomarkers of recurrent and particularly unresectable/metastatic melanoma has been emphasised by…”