Epithelial-mesenchymal transition dysregulation in prostate cancer: Insights from molecular unraveling and epidemiological analyses in Tunisia, North Africa.

Abstract

The progression of prostate cancer (PCa) has been linked worldwide, including in African populations, to the dysregulation of the epithelial-mesenchymal transition (EMT). To clarify the connection among EMT markers, clinicopathological parameters, and epidemiological factors, we analyzed 35 PCa specimens from patients in Tunisia, a country in North Africa, arranged by stages. We also carried out extensive molecular and epidemiological analyses. Significant dysregulation of EMT genes was found, with an overexpression of ZEB-1, Twist, Snail-1, and Vimentin (p<0.05) and underexpression of E-cadherin and β-catenin (p<0.05). Positive correlations were observed between transcription factors and the mesenchymal marker Vimentin (p<0.001, r=0.574; p=0.029, r=0.411; and p<0.001; r=0.506) according to Spearman correlation analyses, whereas negative correlations were found between epithelial markers (E-cadherin, β-catenin) and Vimentin (p<0.05; r<0). Higher PSA, Gleason scores, and metastasis were all correlated with the dysregulation of EMT (p<0.05). Notably, there was a positive correlation between higher consumption of tobacco (≥20 Packets per year) and Vimentin expression (p<0.001, r=0.854), suggesting a relationship between smoking and EMT activation in the Tunisian population. Moreover, Twist showed a positive correlation with diabetes (p<0.001, r=0.385), whereas no significant correlations were found between EMT markers and comorbidities such as hypertension and coronary insufficiency. These results demonstrate the intricate connection between molecular changes, epidemiological factors, and disease progression, and they emphasize the crucial role that EMT plays in promoting PCa aggressiveness in African populations, particularly in Tunisia. In summary, understanding these correlations could help develop focused treatment plans and enhance patient outcomes for PCa management in African settings.