Prognostic Significance of SATB1, SMAD3, Ezrin and β-Catenin in Patients with Pancreatic Adenocarcinoma

The present study aimed to explore the role of SATB1, SMAD3, Ezrin and β-catenin as individual and combined biomarkers for the survival prediction in pancreatic adenocarcinoma (PAC). Notably, this study distinguished for the first time a potential prognostic value of SATB1 corresponding to its subcellular localization in PAC. Immunohistochemical staining on tissue macroarrays, as well as RNA-seq data from public sources, were investigated, and the results correlated with overall survival (OS) and clinicopathological features. The connectivity between the examined factors, as well as their common signaling pathways, were demonstrated by the functional enrichment analysis. Herein, the prognostic ability of cytoplasmic SATB1 in OS analysis was even superior to nuclear SATB1. Both staining patterns tended to have opposite roles in the prognosis of PAC: SATB1c was an independent prognostic factor for poor OS, whereas SATB1n expression reached no statistical significance, but Kaplan–Meier curves separated patients with low expression and adverse prognosis from patients with high expression and favorable prognosis. High levels of SATB1 mRNA appeared as an independent prognostic indicator for better OS. Furthermore, individual expression of SMAD3 or Ezrin, as well as combined expression of SATB1/SMAD3/Ezrin/β-catenin, were associated with OS independently of conventional risk factors, both in our cohort and TCGA dataset. In our series, patients with tumors harboring combined expression of SATB1n-high/SMAD3low/Ezrinlow/β-cateninlow experienced the highest survival rates, while those with SATB1c-present/SMAD3high/Ezrinhigh/β-cateninhigh had the worst survival. In conclusion, protein and/or mRNA expression levels of SATB1, SMAD3, Ezrin and β-catenin may serve as potential prognostic biomarkers for PAC, both as single predictors and even better when combined.