LGALS3 cfDNA methylation in seminal fluid as a novel prostate cancer biomarker outperforming PSA

Author:

Abramovic Irena123ORCID,Pezelj Ivan4,Dumbovic Leo4,Skara Abramovic Lucija123,Vodopic Tonci5,Bulimbasic Stela67,Stimac Goran4,Bulic‐Jakus Floriana13,Kulis Tomislav278,Katusic Bojanac Ana13,Tomas Davor9,Ulamec Monika237910,Sincic Nino12311

Affiliation:

1. Department of Medical Biology University of Zagreb School of Medicine Zagreb Croatia

2. Scientific Group for Research on Epigenetic Biomarkers University of Zagreb School of Medicine Zagreb Croatia

3. Scientific Centre of Excellence for Reproductive & Regenerative Medicine University of Zagreb School of Medicine Zagreb Croatia

4. Department of Urology University Clinical Hospital Center Sestre Milosrdnice Zagreb Croatia

5. Department of Pathology, Cytology and Forensic Medicine Varazdin General Hospital Varazdin Croatia

6. Department of Pathology and Cytology University Hospital Centre Zagreb Zagreb Croatia

7. University of Zagreb School of Medicine Zagreb Croatia

8. Department of Urology University Hospital Center Zagreb Zagreb Croatia

9. Ljudevit Jurak Clinical Department of Pathology & Cytology Sestre Milosrdnice University Clinical Hospital Center Zagreb Croatia

10. Department of Pathology University of Zagreb School of Dental Medicine Zagreb Croatia

11. BIMIS—Biomedical Research Center Salata University of Zagreb School of Medicine Zagreb Croatia

Abstract

AbstractBackgroundThe unmet challenge in prostate cancer (PCa) management is to discriminate it from benign prostate hyperplasia (BPH) due to the lack of specific diagnostic biomarkers. Contemporary research on potential PCa biomarkers is directed toward methylated cell‐free DNA (cfDNA) from liquid biopsies since epigenetic mechanisms are strongly involved in PCa development.MethodsIn the present research, cfDNA methylation of the LGALS3 gene in blood and seminal plasma of PCa and BPH patients was assessed using pyrosequencing, as well as LGALS3 DNA methylation in tissue biopsies. Liquid biopsy samples were taken from patients with clinical suspicion of PCa, who were subsequently divided into two groups, that is, 42 with PCa and 55 with BPH, according to the histopathological analysis.ResultsStatistically significant higher cfDNA methylation of LGALS3 in seminal plasma of BPH than in PCa patients was detected by pyrosequencing. ROC curve analysis showed that it could distinguish PCa and BPH patients with 56.4% sensitivity and 70.4% specificity, while PSA did not differ between the two patient groups. In contrast, there was no statistically significant difference in LGALS3 cfDNA methylation in blood plasma between the two patient groups. In prostate tumor tissue, there was a statistically significant DNA hypermethylation of LGALS3 compared to surrounding nontumor tissue and BPH tissue.ConclusionsThe DNA hypermethylation of the LGALS3 gene represents an event specific to PCa development. In conclusion, LGALS3 cfDNA methylation in seminal fluid discriminates early PCa and BPH presenting itself as a powerful novel PCa biomarker highly outperforming PSA.

Publisher

Wiley

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