Expression And Clinical Significance Of IRE1 In Colon Cancer

ObjectiveTo investigate the expression level of signaling passway IRE1α-XBP1, IRE1β and MUC2 in colon cancer tissues and to analyze their relationship with the clinical features and significance of patients, such as tumor proliferation, clinical stage, invasion and metastasis.MethodsThirty-five curative tissues and biopsies of colon cancer and adjacent normal tissues at more than 5cm away from lesioned tissues were collected from the First Affiliated Hospital of Henan University of Science and Technology from September, 2013 to February, 2014. Immunohistochemical method and Western Blot were used to detect the expression level of IRE1α, IRE1β and MUC2 protein, real-time quantitative PCR(RT-PCR) was used to detect the expression level of IRE1α-XBP1, IRE1β and MUC2 m RNA level, combined with the clinical pathological features, SPSS17.0 software was used for data analysis.Results1. Immunohistochemistry showed positive expression of IRE1β yellow or brown particles, and mainly located in the cytoplasm of colonic epithelial cells. The expression of IRE1β was decreased in colon cancer tissues, compared to adjacent normal tissuess(P<0.05). The same as IRE1β, IRE1α expression showed yellow or brown particles, and mainly located in the cytoplasm of colonic epithelial cells, there was no significant difference in IRE1α expression between colon cancer and adjacent normal mucosa. Expression of MUC2 was strongly decreased in colon cancer tissues compared to normal mucosa. IRE1β expression level was found to be significantly associated with the lymph node metastasis, tumor stages and histological differentiation(P<0.05), but not with the gender and age. IRE1α and MUC2 have been no association with these clinicopathological parameters;2. Western Blot results confirmed a significant reduction of IRE1β protein in colon cancer tissues(P<0.05). IRE1α expression was no change in cancer tissues compared to the paired noncancerous tissues;3. Consistently with protein expression, RT-PCR showed that expression levels of IRE1β m RNA, MUC2 mRNA were lower in colon carcinoma tissuess than that adjacent normal tissues(P<0.05). The expression of IRE1β mRNA, MUC2 mRNA in normal tissuess were 2.1 times and 4.5 times higher than in colon carcinoma tissues. IRE1β expression was found to be significantly associated with tumor stages, lymph node metastasis and tumor differentiation, MUC2 m RNA expression level was related to smoking. IRE1α m RNA and XBP1 mRNA have been no association with these clinicopathological parameters;4. In the correlation analysis, the expression of IRE1β were positively correlated with MUC2.Conclusion1. In colon cancer, the mRNA and protein level of IRE1β was decreased. It was found to be significantly associated with tumor stages, lymph node metastasis and tumor differentiation, which indicated that IRE1β may play an important role in the occurrence and development of colon cancer;2. There was no significant difference in IRE1α and XBP1 expression between colon cancer and adjacent normal tissues, suggesting this signaling pathway may not participate in the pathogenesis of colon cancer;3. The expression of IRE1β and MUC2 were positively correlation in colon cancer, which suggested that IRE1β plays a role in MUC2 expression and both may participate in the pathogenesis of colon cancer.