Expression Analysis of the Mediators of Epithelial to Mesenchymal Transition and Early Risk Assessment of Therapeutic Failure in Laryngeal Carcinoma

Abstract

Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy which lacks early predictors of prognosis. Here, we hypothesized that expression and prognostic characterization of the critical mediators of epithelial to mesenchymal transition (EMT) may provide key information in this regard. Linear regression and multiple correspondence analyses were performed on immunohistochemical data obtained from 20 invasive tumors. Principal component and unsupervised hierarchical clustering were used to analyze the dataset patterns associating with LSCC metastatic profile. Survival and death risk assessments were performed using Kaplan–Meier and hazard ratio tests. Data mining analysis using CHAID decision tree and logistic regression analysis was applied to define the predictive value of the risk factors of tumor aggressiveness. Our analyses showed, that in invasive LSCC tumors, cells associating with a mesenchymal profile were likely to exhibit enhanced NOS2, TGF-β, and IL-17A expression levels, concomitantly to NF-κB nuclear translocation. IHC data deciphering determined that EMT induction was also linked to the enrichment of the tumors with CD68+ populations and IL-10 signal. Strikingly, dataset cluster analysis showed that these signatures could define distinct patterns of invasive tumors, where NOS2 associated with IL-10 expression, and TGF-β and IL-17A signals associated with MMP-9 activation. Decision tree analysis identified IL-17A as a possible predictor of LSCC aggressiveness. Altogether, our results show that distinct immunological patterns would support the acquisition of EMT features in invasive LSCC and suggest that IL-17A may be useful in the early identification of patients “at-risk” of therapeutic failure.

Association of E-cadherin & vimentin expression with clinicopathological parameters in lingual squamous cell carcinomas & their role in incomplete epithelial mesenchymal transition

“…The correlation of E-cadherin expression at the IF with clinicopathological parameters, risk score and lymph node metastasis showed no statistical significance similar to other studies 4 5 12 20 , including parameters such as age, gender, size or stage of the tumour 4 5 12 , worsening pattern of tumour differentiation 3 12 . Based on similar results, it shows that expression of immunomarkers such as E-cadherin may not have an impact on the biological behaviour of these tumours 20 .…”

“…The expression of vimentin at IF showed no correlation in the present study, as was seen in a few other studies that showed similar lack of significant correlation with lymph node metastases 5 12 , age, gender, histological differentiation, POI, size and stage of tumour 5 8 . Contrasting with a positive correlation of Vimentin positivity at IF with lymph node metastasis 8 21 degree of differentiation, clinical stage and POI 19 .…”

“…A significant decrease in E-cadherin at IF compared to CSA has been reported earlier 4 8 19 with a significant gain in vimentin at IF 4 , as in the present study, however, there are contrary reports 5 8 .…”

“…E-cadherin mediates intercellular adhesion and is expressed normally in the stratum spinosum of the oral mucosa 5 . As it maintains the cohesiveness of the cells, its loss or downregulation is associated with the process of EMT 6 .…”

Permissive State of EMT: The Role of Immune Cell Compartment

“…The contact-independent mechanism by which Treg cells control the immune response consist in the production of immunoregulatory cytokines such as IL-10, TGF-β, and IL-35 that have been reported to be correlated with mesenchymal tumor type (45).…”