CRM1 is a novel independent prognostic factor for the poor prognosis of gastric carcinomas

Abstract

Gastric cancer (GC) is a highly aggressive malignant tumor. Its high mortality rate prompts the urgent need for novel therapeutic agents. The aim of this study is to detect the expression of CRM1 in GC, which has not been reported to date. The expression of CRM1 in GC and adjacent noncancerous tissues (ANCT) of gastrectomy specimens from 120 GC patients was measured by immunohistochemistry. In addition, correlations between the CRM1 staining and the clinicopathologic features as well as survival were analyzed. Positive expression rates of CRM1 in GC and ANCT were 57.8 and 6.7%, respectively. High expression of CRM1 was significantly associated with increased serum level of carcinoma embryonic antigen (CEA, P = 0.02) but not associated with that of carbohydrate antigen 19-9 (P = 0.38). CRM1 levels were correlated with more advanced tumor stages (P = 0.01), positive Her2 status (P = 0.01), and distant metastasis (P = 0.02). Univariate analysis showed that CEA (P = 0.0076), TNM stage (P = 0.0001), metastasis (P = 0.027), and CRM1 expression (P = 0.0019) were significant risk factors affecting overall survival of GC patients. The multivariate analysis indicated that the CRM1 was an independent indicator for GC survival (P = 0.0048). The current results indicated that CRM1 expressed in a subpopulation of GC with aggressive behavior and could serve as a prognosis marker for poor outcome.

Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy

“…CRM1 expression is enhanced in many cancer tissues. High expression of CRM1 in gastric, ovarian, and pancreatic cancers show poor prognosis [62][63][64] . The increase in CRM1 leads to cytoplasmic abundance of tumor suppressors and cell cycle regulators, which in turn results in their aberrant activation.…”

Expression of chromosomal regional maintenance protein-1 may be associated with subcellular survivin expression in human gastric and colorectal carcinoma

“…Furthermore, no significant differences in CRM-1 expression rate were identified between gastric carcinomas classified according to tumor type (differentiation status), although expression rates in both the nucleus and cytoplasm were higher in intestinal type gastric carcinomas than diffuse type gastric carcinomas. Zhou et al (23) reported that CRM-1 expression did not correlate with tumor differentiation status (poor vs. well to moderate). The authors also reported a higher CRM-1 expression rate in well to moderately-differentiated gastric adenocarcinomas compared with poorly-differentiated gastric adenocarcinomas (23).…”

“…Zhou et al (23) reported that CRM-1 expression did not correlate with tumor differentiation status (poor vs. well to moderate). The authors also reported a higher CRM-1 expression rate in well to moderately-differentiated gastric adenocarcinomas compared with poorly-differentiated gastric adenocarcinomas (23). These results are consistent with those of the present study and suggest that no association exists between CRM-1 expression and tumor differentiation status in gastric carcinoma.…”

“…High CRM-1 expression has been identified in several malignancies, including stomach, pancreatic, ovarian, cervical, renal and esophageal cancers. Its presence in tumor cells indicates that it predicts an unfavorable prognosis (18)(19)(20)(21)(22)(23).…”

Inhibition of nucleo-cytoplasmic shuttling through XPO1/CRM1: A unique therapeutic approach for treatment of haematological and solid malignancies

“…Overexpression of XPO1 leads to mislocalization of key regulatory proteins and is associated with resistance to chemotherapy, poor prognosis and short survival in many human malignancies [14][15][16] . XPO1 hot mutations (E571) were found in approximately 4% of primary chronic lymphocytic leukemia (CLL) patients [17,18] .…”