cfDNA methylation in liquid biopsies as potential testicular seminoma biomarker.

Background: Seminoma is a testicular tumor type, routinely diagnosed after orchidectomy. As cfDNA represents a source of minimally invasive seminoma patient management, this study aimed to investigate whether cfDNA methylation of six genes from liquid biopsies, have potential as novel seminoma biomarkers. Materials & methods: cfDNA methylation from liquid biopsies was assessed by pyrosequencing and compared with healthy volunteers' samples. Results: Detailed analysis revealed specific CpGs as possible seminoma biomarkers, but receiver operating characteristic curve analysis showed modest diagnostic performance. In an analysis of panels of statistically significant CpGs, two DNA methylation panels emerged as potential seminoma screening panels, one in blood CpG8/CpG9/CpG10 (KITLG) and the other in seminal plasma CpG1(MAGEC2)/CpG1(OCT3/4). Conclusion: The presented data promote the development of liquid biopsy epigenetic biomarkers in the screening of seminoma patients.

Seminoma belongs to testicular cancer, which represents a common malignancy among men of reproductive age. Diagnosis of seminoma is a multistep process that also includes checking tumor biomarkers from blood. However, these biomarkers are not specific for seminoma and to conclude a definite diagnosis of seminoma immunohistochemical analysis is needed, which requires the removal of a whole or partial testicle. Therefore, there is a need for novel, noninvasive biomarkers. cfDNA is the most extensively investigated source of minimally invasive tumor markers. Therefore, this study investigated cfDNA methylation of six genes as potential noninvasive biomarkers for the management of seminoma patients. By examining CpG sites of selected genes by pyrosequencing, the authors detected significant differences. However, receiver operating characteristic curve analysis showed modest results. Therefore, the authors tested possible panels of significantly different CpGs and detected two possible DNA methylation panels for seminoma screening. These findings suggest the further investigation of possible epigenetic biomarkers for seminoma patient management from liquid biopsies.

Epigenomics. 2023 Feb 01 [Epub ahead of print]

Dora Raos, Davor Oršolić, Silvija Mašić, Miroslav Tomić, Jure Krasić, Igor Tomašković, Nora Nikolac Gabaj, Nina Gelo, Željko Kaštelan, Tomislav Kuliš, Ana Katušić Bojanac, Anja Barešić, Monika Ulamec, Davor Ježek, Nino Sincic

University of Zagreb School of Medicine, Department of Medical Biology, 10000 Zagreb, Croatia., Ruđer Bošković Institute, Division of Electronics, Laboratory for Machine Learning & Knowledge Representation, 10000 Zagreb, Croatia., Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, 10000 Zagreb, Croatia., University of Zagreb School of Medicine, Scientific Group for Research on Epigenetic Biomarkers, 10000 Zagreb, Croatia.