TESTICULAR GERM CELL TUMORS: INSIGHTS FROM EPITHELIAL-MESENCHYMAL TRANSITION

Introduction: Germ cell tumors (GCTs) are benign or malignant neoplasms derived from germ cells that can occur in gonadal or extragonadal sites, representing 3,3% of malignant tumors. Testicular GCTs (TGCTs) are organized into two main histological groups, known as seminoma and non-seminoma germ cell tumors (NSGCTs). Seminoma GCTs are made up of undifferentiated germ cells that can histologically resemble sperm and young oogonia. NSGCTs are subdivided into several histologies, such as embryonal carcinoma, yolk sac tumors, teratoma, choriocarcinoma, and mixed NSGCT, in which different histologies are present in different proportions. The molecular mechanism that differentiates each histology is not determined. Among the hallmarks of cancer includes epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their characteristics and acquire mesenchymal phenotype. EMT can be induced by several factors and signaling pathways, including the transcription factors Slug and Snail. EMT has been associated with several types of cancer, however, EMT in GCTs has not yet been elucidated. Objective: Therefore, the aim of this study is to investigate the expression of EMT markers in GCTs. Methods: An in silico analysis was performed using the cBioPortal platform to evaluated the expression of EMT markers (migration, cell differentiation and proliferation, extracellular matrix and adhering molecules, cancer stem cells and signal transduction), as well as Snail and Slug factors, in TGCTs patients. Then, four GCTs lineages (NTERA-2 and 1777N: embryonal carcinoma; JEG-3: choriocarcinoma; and 577MF: mature teratoma) were evaluated for the expression of EMT markers by real-time PCR. Results: Slug factor showed a significant impact on disease-free survival. Assessing the correlation of Snail and Slug expression with markers of biological processes associated with EMT, a positive correlation of Slug with these markers and a negative correlation with Snail were observed. The analyses of Snail and Slug expression by real-time PCR were in accordance with the in silico analyses, in which were presented opposite results in the same lineage. Furthermore, the following markers E-cadherin, TGF-β, Vimentin, Fibronectin, N-cadherin, COL1A1, and a-SMA were analyzed in four lineages and 1777N was the most associated with EMT, with higher expression of Slug. Conclusion: Therefore, the expression of Slug transcription factor is more correlated with EMT in embryonal carcinomas from TGCTs.