Loss of CRNN expression is associated with advanced tumor stage and poor survival in patients with esophageal squamous cell carcinoma

Abstract

CRNN gene expression is downregulated in esophageal squamous cell carcinoma (ESCC), although its clinical implications in esophageal cancer remain unclear. We performed integrated microarray analysis and identified the CRNN gene as 1 of the major downregulated genes in ESCC. CRNN downregulation was validated at the nucleic acid level in 16 ESCC cases using complementary DNA microarray and at the protein level by immunohistochemical stains in an additional 220 ESCC cases. The clinicopathologic relevance and prognostic significance of CRNN expression in ESCC were explored. Downregulated CRNN expression was noted at the messenger RNA and protein levels. Immunohistochemical staining revealed negative and positive CRNN expression in 171 (77.7%) and 49(22.3%) patients with ESCC, respectively. Patients with negative CRNN protein expression had an advanced tumor invasion depth (P=.002), advanced nodal involvement (P=.014), and longer tumor length (P=.037). Patients with negative CRNN expression (median survival, 14.0 months; 5-year survival rate, 20.5%) had pooreroverall survival than those with positive expression (30.0 months and 40.3%, respectively; P=.006). On multivariate analysis, negative CRNN expression, nodal involvement, and distant metastasis remained significant prognostic factors for poor overall survival (negative vs positive CRNN, hazard ratio, 1.464; P=.047). Our analysis has highlighted the clinical implications of CRNN expression in ESCC. Loss of CRNN expression correlated with advanced tumor length, greater tumor invasion depth, lymph node metastasis, and poor survival in patients with ESCC.