High levels of REV7 expression are associated with poor prognosis and chemoresistance in gastric adenocarcinoma

Abstract

REV7 is a multifunctional protein essential for promoting cellular tolerance to DNA damage. REV7 expression is associated with disease progression and prognosis in several human malignant tumors. This study aimed to evaluate the clinical and biological significance of REV7 in gastric adenocarcinoma (GAD). REV7 expression in 167 resected GADs was immunohistochemically assessed and examined the association with clinicopathological features. Positive expression of REV7 was significantly associated with tumor undifferentiation (p < 0.001), lymphatic invasion (p = 0.035), recurrence (p = 0.042), and mortality (p = 0.031). The Kaplan‐Meier curves with log‐rank tests revealed significantly poorer progression‐free survival (p = 0.049), overall survival (p = 0.037), and post‐progression survival (p = 0.038) in the REV7‐positive group. Multivariate analysis using the Cox proportional hazard model identified REV7 as an independent prognostic factor for overall survival (p = 0.028). REV7‐depleted GAD cell lines demonstrated enhanced sensitivity to cisplatin compared with control cells. Additionally, the expression levels of REV7 in residual tumors from surgical specimens of patients who received preoperative chemotherapy were higher than those in samples without chemotherapy (p = 0.029), suggesting that REV7‐positive tumors are chemoresistant. These results indicate that REV7 is a predictive biomarker for the prognosis and chemosensitivity of GAD.