Relationship between the expression of DDX39 protein and prognosis of colorectal cancer

Abstract

To investigate the relationship between the expression of DDX39 protein and prognosis in colorectal cancer. Clinical data and paraffin specimens of postoperative tumor tissue from 824 patients with primary colorectal cancer who received first surgical treatment at the Department of Colorectal Surgery of Changhai Hospital of Navy Military Medical University from January 2010 to December 2011 were collected. Paraffin samples of paracancerous tissues of 38 patients were served as controls. At the same time, samples of normal rectal mucous membrane from 37 cases after procedure of prolapse and hemorrhoids, and samples of colorectal adenoma from 33 cases after endoscopic treatment were enrolled in this study. All the specimens were made as the tissue microarray, and the expression of DDX39 protein was detected by immunohistochemistry. The expression of DDX39 in the epithelium and stroma was evaluated with the average staining intensity (H-Score) and the number of positive cells. It was defined as high expression in the epithelium that the H-Score was greater than or equal to 200. It was defined as high expression in the stroma that the number of positive cells was greater than or equal to 50 in 200 times the field of vision. Relationship of different DDX39 expression levels with clinicopathological parameters and prognosis of colorectal cancer was analyzed. The expression of DDX39 in colorectal cancer tissues was lower than that in normal tissues, paracancerous tissues and adenomatous tissues, whether it is in the epithelium or in the stroma [DDX39 expression in the epithelium: normal tissues 253.2±64.1, paracancerous tissues 238.8±79.2, adenomatous tissues 259.4±51.6, colorectal cancer tissues 194.2±76.5 (P=0.000, P=0.005, P=0.000, respectively); DDX39 expression in the stroma: normal tissues 110.1±64.8, paracancerous tissues 106.0±49.2, adenomatous tissues 108.5±79.1, colorectal cancer tissues 54.1±34.7(all P=0.000)]. Among the cases of colorectal cancer, there were 541 cases of high DDX39 expression and 283 cases of low DDX39 expression in the epithelium; there were 424 cases of high DDX39 expression of and 400 cases of low DDX39 expression in the stroma. The high DDX39 expression and low DDX39 expression in epithelial and stromal of colorectal cancer were related respectively with tumor location (P=0.006, P=0.016), degree of tumor differentiation (P=0.002, P=0.064), TNM stage (P=0.021, P=0.000), serum CEA level (P=0.003, P=0.005), serum CA199 level (P=0.040, P=0.005) and tumor recurrence and metastasis (P=0.000, P=0.000). All the colorectal cancer cases were followed up for (41.6±15.7) months after operation. The 5-year overall survival (OS) and disease-free survival (DFS) rates of the cases with epithelial low DDX39 expression were 84.1% and 61.5%, and both were significantly lower as compared to those with epithelial high DDX39 expression (95.4% and 88.2%, P=0.000, P=0.000). The 5-year OS and DFS rates of the stroma low DDX39 expression were 86.8% and 66.8%, and both were significantly lower as compared to those with stroma high DDX39 expression (96.1% and 90.6%, P=0.000, P=0.000). Cox multivariate analysis showed that tumor differentiation (OS:HR=0.252, 95%CI: 0.128 to 0.497, P=0.000; DFS:HR=0.266, 95%CI: 0.134 to 0.530, P=0.000), DDX39 expression level in epithelium (OS: HR =0.229, 95%CI: 0.138 to 0.382, P=0.000; DFS: HR =0.266, 95%CI: 0.158 to 0.446, P=0.000), and DDX39 expression level in stroma (OS: HR =0.331, 95%CI: 0.188 to 0.582, P=0.000; DFS:HR=0.326, 95%CI: 0.184 to 0.578, P=0.000) were independent influencing factors of overall or disease-free survival in patients with colorectal cancer. The low expression of DDX39 protein suggests poor prognosis and DDX39 is expected to be a new prognostic marker of colorectal cancer.