Clinicopathological and Prognostic Implications of Epithelial-to-Mesenchymal Transition-Related Immunohistochemical Markers in Resectable Pancreatic Cancer: A Retrospective Longitudinal Study.
Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of global cancer death. The process of epithelial-to-mesenchymal transition (EMT) is a key driver of early progression and metastasis in PDAC.
Our study aimed to explore the correlation between the expression of EMT markers and survival outcomes.
We conducted a retrospective longitudinal study on patients diagnosed with resectable PDAC between January 2005 and June 2019, with a 5-year follow-up for survival analysis. Immunohistochemical staining was performed to assess E-cadherin and vimentin expression. EMT was defined as the presence of high Vimentin (mesenchymal) expression combined with low E-cadherin (epithelial) expression. The study cohort included 135 patients with resectable PDAC, with 86 males (63.7%) and a mean age of 63.5 years (SD 10.1); most tumors were grade 2 (84, 64.6%). Cox regression analysis revealed that Vimentin expression (p = 0.005), positive margin (p = 0.008), and absence of metformin intake (p = 0.023) were independent predictors of poor OS. High Vimentin was associated with lower median OS (17.0 ± 4.4 vs. 25.8 ± 2.3 months, p = 0.037) and DFS (8.6 ± 1.2 vs. 13.0 ± 2.3 months, p = 0.014), compared to low Vimentin, and it was correlated with higher tumor grade (p = 0.028) and metastasis rate (p = 0.032). The poorest outcomes were observed when high Vimentin was coupled with low E-cadherin (median OS of 12.6 ± 4.7 vs. 24.5 ± 2.1 months, p = 0.038; median DFS of 9.5 ± 0.5 vs. 10.8 ± 2.1 months, p = 0.029), compared to the rest of the population.
Our findings showed that Vimentin overexpression and the EMT phenomenon are strongly associated with poor OS and DFS in resectable PDAC, underscoring their potential as prognostic biomarkers and therapeutic targets.
Our study aimed to explore the correlation between the expression of EMT markers and survival outcomes.
We conducted a retrospective longitudinal study on patients diagnosed with resectable PDAC between January 2005 and June 2019, with a 5-year follow-up for survival analysis. Immunohistochemical staining was performed to assess E-cadherin and vimentin expression. EMT was defined as the presence of high Vimentin (mesenchymal) expression combined with low E-cadherin (epithelial) expression. The study cohort included 135 patients with resectable PDAC, with 86 males (63.7%) and a mean age of 63.5 years (SD 10.1); most tumors were grade 2 (84, 64.6%). Cox regression analysis revealed that Vimentin expression (p = 0.005), positive margin (p = 0.008), and absence of metformin intake (p = 0.023) were independent predictors of poor OS. High Vimentin was associated with lower median OS (17.0 ± 4.4 vs. 25.8 ± 2.3 months, p = 0.037) and DFS (8.6 ± 1.2 vs. 13.0 ± 2.3 months, p = 0.014), compared to low Vimentin, and it was correlated with higher tumor grade (p = 0.028) and metastasis rate (p = 0.032). The poorest outcomes were observed when high Vimentin was coupled with low E-cadherin (median OS of 12.6 ± 4.7 vs. 24.5 ± 2.1 months, p = 0.038; median DFS of 9.5 ± 0.5 vs. 10.8 ± 2.1 months, p = 0.029), compared to the rest of the population.
Our findings showed that Vimentin overexpression and the EMT phenomenon are strongly associated with poor OS and DFS in resectable PDAC, underscoring their potential as prognostic biomarkers and therapeutic targets.
Authors
Machmouchi Machmouchi, Zahreddine Zahreddine, Aoun Aoun, Abbas Abbas, Charafeddine Charafeddine, Chehade Chehade, Elias Elias, El Husseini El Husseini, Temraz Temraz, Mukherji Mukherji, Khalife Khalife, Faraj Faraj, Zaidan Zaidan, Kadi Kadi, Tawil Tawil, Shamseddine Shamseddine
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