Testicular Germ Cell Tumor Tissue Biomarker Analysis: A Comparison of Human Protein Atlas and Individual Testicular Germ Cell Tumor Component Immunohistochemistry

Author:

Krasic Jure12ORCID,Skara Abramovic Lucija23ORCID,Himelreich Peric Marta24ORCID,Vanjorek Vedran2,Gangur Marko2ORCID,Zovko Dragana2,Malnar Marina2,Masic Silvija5,Demirovic Alma256,Juric Bernardica5,Ulamec Monika257ORCID,Coric Marijana28,Jezek Davor29ORCID,Kulis Tomislav21011ORCID,Sincic Nino212ORCID

Affiliation:

1. Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

2. Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

3. Department of Virology, Croatian Institute of Public Health, 10000 Zagreb, Croatia

4. Health Centre Zagreb–West, 10000 Zagreb, Croatia

5. Ljudevit Jurak Clinical Department of Pathology and Cytology, University Clinical Hospital Center Sestre Milosrdnice, 10000 Zagreb, Croatia

6. School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia

7. Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

8. Department of Pathology and Cytology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia

9. Department of Histology and Embryology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

10. Department of Urology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia

11. Department of Urology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

12. Department of Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

Abstract

The accurate management of testicular germ cell tumors (TGCTs) depends on identifying the individual histological tumor components. Currently available data on protein expression in TGCTs are limited. The human protein atlas (HPA) is a comprehensive resource presenting the expression and localization of proteins across tissue types and diseases. In this study, we have compared the data from the HPA with our in-house immunohistochemistry on core TGCT diagnostic genes to test reliability and potential biomarker genes. We have compared the protein expression of 15 genes in TGCT patients and non-neoplastic testicles with the data from the HPA. Protein expression was converted into diagnostic positivity. Our study discovered discrepancies in three of the six core TGCT diagnostic genes, POU5F1, KIT and SOX17 in HPA. DPPA3, CALCA and TDGF1 were presented as potential novel TGCT biomarkers. MGMT was confirmed while RASSF1 and PRSS21 were identified as biomarkers of healthy testicular tissue. Finally, SALL4, SOX17, RASSF1 and PRSS21 dysregulation in the surrounding testicular tissue with complete preserved spermatogenesis of TGCT patients was detected, a potential early sign of neoplastic transformation. We highlight the importance of a multidisciplinary collaborative approach to fully understand the protein landscape of human testis and its pathologies.

Funder

European Regional Development Fund

Publisher

MDPI AG

Subject

General Medicine

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