The prognostic marker elastin correlates with epithelial-mesenchymal transition and vimentin-positive fibroblasts in gastric cancer.

Abstract

Elastin (ELN) fibers are essential constituents of the tumor microenvironment of gastric cancer (GC). However, few studies have investigated the clinical prognostic significance of ELN in GC. We screened for molecular markers that were highly related to distant metastasis by transcriptome sequencing. The Cancer Genome Atlas (TCGA) and Harbin Medical University (HMU) validation cohorts were used to validate ELN expression and to explore molecular mechanisms. Immunohistochemistry for ELN, vimentin (VIM), and fibroblast activation protein, and elastic fiber-specific staining were used to evaluate the relationship between ELN and prognosis. R studio was used to construct a nomogram prognostic model. In this study, we found that ELN mRNA levels were significantly higher in cancer tissues and were associated with poor prognosis in TCGA and HMU patients. Gene set enrichment analysis showed that ELN was mainly enriched in the epithelial-mesenchymal transition (EMT) pathway. The mRNA expression of ELN was positively correlated with fibroblast molecular markers, especially VIM. For validation, we collected a tissue microarray containing 180 pairs of samples. We found that ELN was positively correlated with VIM expression in cancer tissue but not in paracancerous tissues by immunohistochemistry staining. Univariate and multivariate analyses showed that the expression of ELN and lymph node metastasis rate were independent predictors for overall survival. Moreover, a nomogram model was used to evaluate the risk of death by combining the expression of ELN and lymph node metastasis rate. ELN may play an important role in the progression of GC by regulating EMT and is a useful prognostic indicator in predicting the prognosis of GC.