| Objective To detect mRNA levels of Notch receptors in specimens organization of gastric cancer patients (cancer tissues, adjacent tissues and normal gastric mucosa) by RT-PCR technology, and to detect the expression levels of Notch receptors by immunohistochemical techniques, to analysis the relationship between of the express of these molecules and gastric cancerclinicopathological parameters, clearing the difference of Notch receptors activation in gastric cancer. To privde new molecular mechanism and the basis theoretical mechanism about the relationship between Notch signal pathway and gastric cancer, and new ideas for targeted molecular therapy of gastric cancer.Methods1. Specimen collection Collected postoperative specimens of tissue from April2010to June2010, the Second Hospital of Lanzhou University and Lanzhou Military General Hospital, General SurgeryGastnc Cancer, no preoperative chemotherapy and radiotherapy history. Each patient were cut gastric cancer tissue(confinmed by pathology), adjacent tissue(5cm away from cancer tissue by view of eye) and normal tissue, a total of50patients,150cases of tissue samples. The clinical and pathological diagnostic criteria and TNM staging according toInternational Union Against Cancer (UICC)/Federation of United States cancer (AJCC)2010Edition.2. Method To detect mRNA levels and the expression levels of of Notch receptors in specimens organization of gastric cancer patients (cancer tissues, adjacent tissues and normal gastric mucosa) by RT-PCR technology and by immunohistochemical techniques, to analysis the relationship between of the express of these molecules and gastric cancerclinicopathological parametersResults1. The results of RT-PCR The expression of mRNA levels in Notch receptors (1to4) of the cancer tissue of50patients with gastric cancer by RT-PCR were13.5026±0.3459,21.2588±0.1332,7.6472±0.1592and3.3330±0.0891, were significantly higher than the normal gastric mucosa1(P＜0.05); the expression of mRNA in Notch receptors with adjacent tissues were4.0186±0.1287,9.8389±0.091,2.0958±0.315and1.8329±0.2341, Notch1and Notch2receptors was significantly higher than the normal gastric mucosa(.P＜0.05), the differences of Notch3and Notch4between adjacent tissues and normal gastric mucosa was not ststically significant(P>0.05).2. The results of Immunohistochemistry The positive expression rate of Notch receptors(1-4) showing a trend of increasing from normal gastric mucosa to gastric cancer tissue, there were significant differences among the groups(P=0.000).It is found that the expression of Notchl-4in gastric cancer tissue was significantly higher than the adjacent tissues and normal gastric mucosa(P=0.000,), but the expression of Notch1-4was not significantly differences between the adjacent tissues and normal gastric mucosa(P>0.05).The expression of protein of Notch receptors(1-4) in gastric cancer tissues have nothing to do with patient gender, age, tumor location and size(P>0.05).But the expression of protein of Notch receptors(1-4) in gastric cancer tissues have correlation with clinical pathological features:there are significant differences of Notchl and Notch2between the different gastric cancer and differentiation levels(P=0.001), the expression of Notchl and Notch2in highly, middlely differentiated group(75.86%)were significantly lower than the poorly differentiated group(95.24%, P=0.001), the lower the degree of differentiation, the higher the expression of Notch1and Notch2, both of were negative correlation(rs=-0.382P=0.001; rs=-0.417P=0.001). There was also significant differences on the expression of Notch1and Notch2between different TNM stages(P=0.001), the expression of Notch1and Notch2(55.56%)on the stage of TNM(Ⅰ+Ⅱ)was significant lower than the stage of TNM(Ⅲ+Ⅳ)(90.24%, P=0.024), from the stage of TNM Ⅰ to Ⅳ, the expression gradually increased, and both of were positive correlation,(rs=0.355P=0.001); there were no significant differences about the expression of Notch3, Notch4between gastric cancer histological grade and TNM stages(P>0.05). The expression of Notch (1-4) with lymph node metastasis(96.0%)was higher than without lymph node metastasis(0%, P=0.023), and both of were positive correlation(r s=0.264P=0.03).Conclusion The expression of mRNA and proteins on Notch receptors(1-4) showing a trend of increasing from normal gastric mucosa to gastric cancer tissue, and closely related to the degree of differentiation in gastric cancer, TNM stages and lymph node metastasis. This suggests that the tumor promotion of Notch signal transduction pathway in the process of gastric cancer, Which Notch1and Notch2may play an important role development and progression of gastric cancer. |
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