Gastric Adenocarcinoma Biomarker Expression Profiles and their Prognostic Value

Abstract

Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis. The results demonstrated that ALDH1A and ARID1A may be strong independent prognostic factors associated with overall survival and recurrence-free survival (p < 0.01 and p < 0.05, respectively). Our results demonstrated that ALDH1, CD44, ARID1A, and CAIX in immunoreactive GA tumor cells exhibit different expression profiles compared with control cells and that these differences are associated with patient survival. The molecules with differential expression profiles were associated with some common functions, including hypoxia, epithelial-to-mesenchymal transition, and SW1/SNF-mediated chromatin remodeling. In addition, the loss of ALDH1, ARID1A, and CD44 and the overexpression of CAIX are important for tumor invasion and metastasis; therefore, they may serve as useful prognostic indicators of long-term survival in patients with GA. In conclusion, our study found that abnormal expression of some of the proteins evaluated in GA tumor cells might have an important role in carcinogenesis and tumor progression and thus may influence the prognosis of patients with GA.