Decreased Expression of Cell Adhesion Molecule 4 in Gastric Adenocarcinoma and Its Prognostic Implications.

Cell adhesion molecule 4 (CADM4) is a novel tumor suppressor candidate. The prognostic implications of CADM4 in gastric cancer have not been conclusively elucidated. Therefore, we evaluated the clinicopathological significance and prognostic value of CADM4 expression in a large series of patients with gastric adenocarcinoma. Immunohistochemical staining for CADM4 was performed on 534 gastric adenocarcinomas. We evaluated the associations between CADM4 expression and the clinicopathological and molecular characteristics of the adenocarcinomas. The prognostic effect of CADM4 expression was evaluated by survival analyses. Low CADM4 expression was significantly associated with young age (p = 0.046), aggressive histological type (p < 0.001), high pT category (p < 0.001), nodal metastasis (p < 0.001), high stage (p = 0.002), lymphovascular invasion (p = 0.001), and perineural invasion (p = 0.001). Low CADM4 expression was more frequently observed in tumors without human epidermal growth factor receptor 2 (HER2) amplification (p = 0.002). Low CADM4 expression was associated with worse overall survival (p = 0.007) and recurrence-free survival (p = 0.005) in the survival analyses. Low CADM4 expression was associated with aggressive clinicopathological features and poor clinical outcomes. CADM4 can act as a tumor suppressor in gastric adenocarcinoma and can be considered a prognostic biomarker.