engleski

Novel seminoma biomarker from liquid biopsies

eminoma (SE) is a type of testicular tumour, routinely diagnosed after surgical orchidectomy using tissue analysis by immunohistochemistry of differentially expressed protein markers. Cell- free DNA (cfDNA) is a promising molecular biology platform for noninvasive SE screening and monitoring. We aimed to investigate cfDNA methylation of SE tissue biomarker OCT3/4 in liquid biopsies and determine whether OCT3/4 could be translated to a liquid biopsy approach. To that end, for cfDNA analysis, twenty-four SE patients and thirty-five healthy volunteers from the general population were recruited. For genomic DNA (gDNA) analysis, SE tissue from recruited patient was sampled and testicular tissue samples of twelve patients with non-malignant diagnoses were retrieved from paraffin tissue archive, as a control group. DNA methylation of OCT3/4 was analysed by pyrosequencing in gDNA from SE tissue and cfDNA from blood and seminal plasma. In addition, OCT3/4 expression analysis was performed by immunohistochemistry followed by morphometric analysis. Associations between protein expression and DNA methylation were assessed, and predictive power of DNA methylation between SE and controls was determined using receiver operating characteristic (ROC) curve. OCT3/4 gDNA methylation was in line with its protein expression in SE. In blood plasma, DNA methylation of OCT3/4 was determined as a possible biomarker for SE patient monitoring, while in seminal plasma OCT3/4 methylation was detected as possible screening biomarker. Further analysis revealed only CpG1 site in seminal plasma as potential screening biomarker with detected sensitivity of 100% and specificity of 55%, corresponding to an AUC of 0.71. However, statistically significant CpG1 site detected in blood showed modest diagnostic performance. In conclusion, for the first time, we disclosed that cfDNA methylation of SE tissue biomarker OCT3/4 has great potential as epigenetic biomarkers from liquid biopsy in SE diagnostics.

seminoma ; biomarker ; liquid biopsy

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