| BackgroundGastric cancer is the fourth common cancer wideword,over70%of new cases and deaths occur in developing countries. In china,gastric cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death,the incidence rate is29.9/100thousand and the mortality rate is22.3/100thousand. Environmental risk factors include Helicobacter pylori infection,smoking,high salt intake,and other dietary factors.Patients with a family history of non-hereditary gastric cancer have a higher risk of developing gastric cancer.In a limited number of patients(1%-3%),its diagnosis is associated with inherited syndromes.The ubiquitin-proteasome system(UPS) is a multi-subunit pathway that allows for ubiquitin modification of proteins and leads to either degradation or other non-proteolytic processes such as trafficking or transcriptional activation.Given its role as a regulator of cellular homeostasis it is not surprising that members of the UPS are frequently aberrantly expressed in a number of disease states including cancer.The F-box protein,FBXW7(also known as Sel-10,Ago,Hcdc4) is one member of the UPS,FBXW7targets several oncoproteins,including cyclin E,c-myc,c-jun,Notch1and Notch4for degradation and its tumor suppressor function is thought to be exerted through these substrates.Mutations that disrupt FBXW7are expected to deregulate cyclin E,c-myc,c-jun and Notch signaling thus simultaneously deregulating cell division,cell growth,apoptosis and cell differentiation. ObjectiveTo investigate the expression and clinical significance of FBXW7and Cyclin E in gastric carcinoma.Materials and methods1. Seventy-five pathologically confirmed and surgically resected gastric cancer samples,and twenty-five para-carcinoma normal mucosa tissue samples were chosen..All patients were not receiving preoperative radiotherapy, chemotherapy or biological targeted therapy. Pa thomorphology classification:65cases of adenocarcinoma,10cases of signet ring cell carcinoma;Pathological grade:15cases of well-differentiated carcinoma,26cases of moderately differentiated carcinoma,34cases of poorly differentiated carcinoma and signet ring cell carcinoma; Lymph node metastasis:35cases with no lymph node metastasis,40cases with lymph node metastasis;Clinical staging were done according to the TNM staging standard that published by the American Joint Committee on Cancer (AJCC) in2010:24cases of stage Ⅰ and stage Ⅱ,51cases of stage Ⅲ and stage Ⅳ.2. SP immunohistochemistry method was used to examine the expression of FBXW7and cyclin E in the gastric carcinoma and para-carcinoma normal mucosa tissue.The clinicopatholoic parameters of gastric carcinoma and the correlation between them were analyzed,and the significance of the two indicators were explored in the development of gastric carcinoma.3. Statistical analysis:All the data were analyzed by SPSS17.0software.Chi-square test was used to analyze the date.The correlation of FBXW7and Cyclin E was analyzed with Spearman rank correlation.Test levea=0.05.ResultsThe positive rates of FBXW7in gastric carcinoma and normal tissues were46.7%and84.0%,respectively,with significant difference found between the gastric carcinoma and normal mucosa tissues (χ2=10.606, P=0.001),and FBXW7expression was significantly correlated with the differentiation degree (χ2=7.440,P=0.006),lymphatic metastasis (χ2=4.688, P=0.030) and the clinical stage (χ2=4.601, P=0.032). the positive rate of Cyclin E expression in gastric carcinoma and normal tissues were56.0%and24.0%, respectively, with significant difference found between the gastric carcinoma and normal mucosa tissues (χ2=7.692,P=0.006),and Cyclin E expression was significantly correlated with tumor depth (χ2=4.902, P=0.027),lymphatic metastasis (χ2=4.601,P=0.032)and clinical stage (χ2=4.408, P=0.036).FBXW7expression was negatively correlated with that of Cyclin E (r=-0.517, P=0.000).Conclusion1. The expression of FBXW7in para-carcinoma normal mucosa tissue was significantly higher than gastric carcinoma.and FBXW7expression was significantly correlated with the differentiation degree, lymphatic metastasis and the clinical stage.2. The expression of Cyclin E in gastric carcinoma was significantly higher than para-carcinoma normal mucosa tissue.and Cyclin E expression was significantly correlated with tumor depth, lymphatic metastasis and clinical stage.3. FBXW7expression was negatively correlated with that of Cyclin E. |
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