Deciphering the prognostic significance and regulatory networks of ZEB1 and ZEB2 in prostate adenocarcinoma

Abstract

Aim: Prostate adenocarcinoma (PRAD), a prevalent malignancy affecting men globally, represents a complex interplay of genetic, epigenetic, and microenvironmental influences. Uncontrolled expression of Zinc finger E-box-binding homeobox (ZEB) genes lead to uncontrolled cell division, a characteristic feature of malignancy and cause to evading immune surveillance and establishing a pro-tumorigenic microenvironment. This study aimed to comprehensively investigate the prognostic significance and regulatory roles of ZEB1 and ZEB2 in PRAD.

Method: Bioinformatic analyses utilizing TCGA database data and validation with TCGA-PRAD patient datasets were conducted. Expression patterns of ZEB1 and ZEB2 across cancers were explored, followed by survival analyses in PRAD. The association with clinical parameters, such as Gleason score, metastasis, and TP53 mutation, was investigated using the UALCAN and GEPIA databases. Protein expression was validated through the Human Protein Atlas. A protein-protein interaction (PPI) network analysis elucidated regulatory landscapes.

Results: ZEB1 and ZEB2 showed diverse expression across cancers, with decreased expression in PRAD. Survival analyses confirmed their prognostic relevance in PRAD. Correlation with Gleason score and metastasis highlighted their clinical significance. Protein expression analyses and PPI networks revealed interconnected regulatory pathways involving ZEB1 and ZEB2.

Conclusion: This study unveils ZEB family as potential prognostic markers for PRAD, shedding light on their complex roles in cancer biology. The identified regulatory pathways offer therapeutic targets for disrupting ZEB-mediated processes, suggesting avenues for PRAD treatment. These findings contribute to understanding the intricate landscape of ZEB family in prostate cancer and other malignancies.