Investigating the role of FKBP4 in testis germ cell tumor via integrated in silico approach.

Testis Germ Cell Tumor (TGCT) is a most common type of testicular malignancy (95%), manifesting mostly in adult men. In recent studies, TGCT have been characterized by aneuploidy, less alteration in genome and low levels of methylation, apart from pathological characterization. Expression of Cancer- Testis (CT) genes in TGCT have also been observed in tumors arising from non-germ cells. Datasets from different online tools showed that expression of FKBP4 have significant difference in TGCT as compared to the normal testis tissues. In addition, FKBP4 showed increased expression with successive stages of TGCT. The FKBP4 showed positive correlation with SALL4, NANOG, SOX2, OCT4, PRSS21 while negative correlation with MGMT, RASSF1, SOX17 and KIT. Analysis showed the increased hazard ratio (HR) is case of overall survival (OS) as compared to the disease-free survival (DFS) in TGCT patient. Furthermore, gene ontology enrichment analysis was performed with upregulated genes in TGCT using DAVID database. FKBP4 belongs to families of peptidyl proline cis-trans isomerase (PPIase), which catalyses the cis-trans isomerization in peptide bonds which comes before proline. PPIases are engaged in numerous cellular processes, and when these processes go awry, can cause both neoplastic and degenerative disorders. To decipher the pathway regulating the proliferation of TGCT, FKBP4 interaction analysis was conducted using STRING, which shows the interaction with known biomarkers of TGCT. All this dataset of expression profile, correlation, and interaction analysis represents FKBP4 might act as a key player to differentiate subtype of Testis Germ Cell Tumor (TGCT). The online version contains supplementary material available at 10.1007/s40203-026-00592-w.