CD44, CDH6, ITGAV, and SERPINE1 are Epithelial‒MesenchymalTransition Markers in Gastric Cancer

Introduction: The Epithelial‒Mesenchymal Transition (EMT) is correlated with poor prognosis in patients with Gastric Cancer (GC). Traditional EMT markers are quantified to identify the activated processes. However, these molecules are not universally present. Thus, identifying more representative EMT markers is important for a better understanding of the EMT process, metastasis, and the progression of GC. Methods: Univariate Cox analysis was performed to identify the EMT-related genes associated with GC prognosis. Lasso Cox analysis was further applied to identify candidate genes and generate a signature to predict the overall survival of GC patients. Then, EMT and non-EMT groups were established in GC cell lines to compare candidate gene expression levels. Finally, the associations between the expression levels of the candidates and TNM stage were explored by using immunohistochemistry (IHC) and the UALCAN database. Results: From a total of 200 EMT-related genes, 47 EMT-related genes associated with GC prognosis were identified. Subsequently, 12 EMT-related genes were selected as candidates to predict the overall survival of patients with GC. The 12-gene signature demonstrated strong predictive performance. Furthermore, in vitro analysis revealed that the expression levels of CD44, CDH6, ITGAV, and SERPINE1 were upregulated in the EMT group. In addition, the expression levels of CD44, CDH6, ITGAV, and SERPINE1 were associated with TNM stage. Discussion: The 12-gene signature was validated to be an independent prognostic factor for GC, highlighting its potential predictive ability, and these genes are more likely to be EMT markers in GC. Future studies are warranted to confirm the predictive performance of the 12-gene signature in larger population samples. CD44, CDH6, ITGAV, and SERPINE1 were identified as EMT markers in an in vitro model, which is conducive to a comprehensive understanding of EMT. However, these findings should be validated in an in vivo model in subsequent studies. Conclusion: CD44, CDH6, ITGAV, and SERPINE1 are strongly related to GC prognosis and may be useful EMT markers in GC.