Expression And Significance Of AnnexinⅡ, NF-κBp65 And VEGF-C In The Tissue Of Gastric Carcinoma

Backgroud and objective:Gastric carcinoma is one of common gastrointestinal malignant tumor in China. Its morbidity and mortality rates increased year by year. Invasion and metastasis is an important factor affecting the prognosis. Many studies have shown that the occurrence and development of gastric carcinoma is a multi-gene effects, multiple steps of the complex process. Many genes and their protein products involved in the occurrence, development, invasion and metastasis of gastric carcinoma. AnnexinⅡis a calcium-dependent phospholipid-binding protein. It participates in a series of cellular events such as membrane aggregation, ion channel formation, the process of exocytosis and endocytosis, RNA binding, DNA synthesis, cell proliferation and apoptosis, etc. In addition, AnnexinⅡpromotes the generation of plasmin and pre-cathepsin B as a receptor, promotes the degradation of extracellular matrix and plays an important role in the process of the tumor's occurrence, invasion and metastasis. NF-κB (nuclear factor-kappaB) is an important multi-tropism of nuclear transcription factor, which can regulate a lot of tumor-related gene's transcription. There is abnormal activation in a lot of tumor tissues. P50/P65 heterodimers are the major activation form. It promotes the occurrence, invasion and metastasis of the tumor through upregulating cell proliferation-related genes,upregulating anti-apoptosis gene, increasing the expression of the proteins and cytokines associated with cell adhesion, matrix degradation and migration. Vascular endothelial growth factor is a group of important pro-angiogenic factors, including a lot of subtypes, in which VEGF-C also can promote the formation of lymphatic vessels in addition to induce angiogenesis. VEGF acts on vascular endothelial cells directly to stimulate the proliferation of tumor cells which can provide nutrition for the tumor cells; it also increases the permeability of vascular endothelial cells to make plasma fibrin and other important factors extravasate, which can create conditions for tumor cells'invasion and metastasis.About the united detection of AnnexinⅡ, NF-κBp65, VEGF-C protein in gastric carcinoma and the research of its relationship with the invasion and metastasis, there has not been reported in the literature yet both at home and abroad. In order to further discuss the relationship between the AnnexinⅡ, NF-κBp65, VEGF-C protein and the invasion and metastasis of gastric carcinoma, search for an early indicator to detect the occurrence, development, invasion, metastasis of the gastric carcinoma and explore new target for treatment, our research adopts immunohistochemistry SP to detect the expression of AnnexinⅡ, NF-κBp65, VEGF-C protein in gastric adenocarcinoma tissues of 33 cases, atrophic gastritis tissues of 20 cases and normal tissues of 33 cases respectively and explores their relationship from each other and mechanism of action. The aim is to clarify the role of these three proteins in the occurrence, development, invasion and metastasis of gastric carcinoma, and to provide a theoretical basis for the clinical treatment of gastric carcinoma.Material and methods:1.Using the technology of immunohistochemistry SP to detect the expression of AnnexinⅡ, NF-κBp65 and VEGF-C protein in the 33 cases of gastric adenocarcinoma tissues,20 cases of atrophic gastritis tissues and 33 cases of normal tissues respectively. 2.Statistical analysis:All the datas were analyzed by SPSS17.0 statistical software package. The comparison of positive rates uses the Chi-square; the correlation of two variable are analyzed by the Spearman's correlation analysis. The level of significant difference is a=0.05.Results:1. the positive expression rate of AnnexinⅡprotein was 81.82%(27/33)in gastric adenocarcinoma tissues,45.00%(9/20) in atrophic gastritis tissues and 24.24%(8/33) in normal tissues. The positive expression rate of AnnexinⅡprotein in gastric adenocarcinoma was significantly more than that in atrophic gastritis tissues and normal tissues, and the difference were statistically significant (P<0.05). The comparison between atrophic gastritis tissues and normal tissues was not statistically significant(P>0.05). With the reduction in the degree of differentiation of gastric carcinoma, AnnexinⅡprotein's positive expression rate was gradually increased, in well-differentiated adenocarcinoma was 76.47%(13/17), in the poorly differentiated adenocarcinoma was 87.50%(14/16), but the difference was not statistically significant(P>0.05). With the inereasing of infiltrating depth of gastric carcinoma, AnnexinⅡprotein's positive expression rate was gradually increased, in which infiltrated deep mussel layer and above of 75.00%(9/12), in which infiltrated all layers of 85.71%(18/21), but the difference was not statistically significant too(P> 0.05). The positive expression rate of AnnexinⅡprotein in gastric cancer with lymph node metastasis was 95.00%(19/20), significantly increased than that without lymph node metastasis group (61.54%,8/13), the difference was statistically significant (P< 0.05).2. the positive expression rate of NF-κBp65 protein was 75.76%(25/33) in gastric adenocarcinoma tissues,40.00%(8/20) in atrophic gastritis tissues and 15.15%(5/33) in normal tissues. The comparison between the gastric adenocarcinoma tissues and the atrophic gastritis tissues,the gastric adenocarcinoma tissues and the normal tissues,the atrophic gastritis tissues and the normal tissues were statistically significant (P<0.05). With the reduction in the degree of differentiation of gastric carcinoma, NF-κBp65 protein's positive expression rate was gradually increased, in well-differentiated adenocarcinoma was 58.82%(10/17), in the poorly differentiated adenocarcinoma was 93.75%(15/16), and the difference was statistically significant (P<0.05). With the inereasing of infiltrating depth of gastric carcinoma, NF-κBp65 protein's positive expression rate was gradually increased, in which infiltrated deep mussel layer and above of 75.00%(9/12), in which infiltrated all layers of 76.19%(16/21), but the difference was not statistically significant(P>0.05). The positive expression rate of NF-KBp65 protein in gastric cancer with lymph node metastasis was 90.00%(18/20), significantly increased than that without lymph node metastasis group (53.85%,7/13), and the difference was statistically significant (P< 0.05).3. the positive expression rate of VEGF-C protein was 78.79%(26/33) in gastric adenocarcinoma tissues,30%(6/20)in atrophic gastritis tissues and 27.27%(9/33) in normal tissues. The positive expression rate of VEGF-C protein in gastric adenocarcinoma significantly more than that in atrophic gastritis tissues and normal tissues, and the difference was statistically significant (P<0.05). The comparison between atrophic gastritis tissues and normal tissues was not statistically significant(P >0.05). With the reduction in the degree of differentiation of gastric carcinoma, VEGF-C protein's positive expression rate was gradually increased, in well-differentiated adenocarcinoma was 64.71%(11/17), in the poorly differentiated adenocarcinoma was 93.75%(15/16), and the difference was statistically significant (P<0.05). With the increasing of infiltrating depth of gastric carcinoma, VEGF-C protein's positive expression rate was gradually increased, in which infiltrated deep mussel layer and above of 66.67%(8/12), in which infiltrated all layers of 85.71% (18/21), but the difference was not statistically;significant(P>0.05). The positive expression rate of VEGF-C protein in gastric cancer with lymph node metastasis was 95.00%(19/20), significantly increased than that without lymph node metastasis group (53.85%,7/13), and the difference was statistically significant (P<0.05).4. There is a positive correlation between the expression of AnnexinⅡprotein and NF-κBp65 protein in gastric carcinoma tissues. (γ=0.467, P<0.05)5. There is a positive correlation between the expression of AnnexinⅡprotein and VEGF-C protein in gastric carcinoma tissues. (γ=0.524, P<0.05) 6. There is a positive correlation between the expression of NF-KBp65 protein and VEGF-C protein in gastric carcinoma tissues. (γ=0.398, P<0.05)Conclusions:1. The positive expression rates of AnnexinⅡ, NF-κBp65, VEGF-C protein have gradually increased from normal tissues, atrophic gastritis tissues to gastric adenocarcinoma tissues, and there are significant differences amony these three groups. It suggests that these three proteins may be involved in the process of gastric carcinoma occurrence.2. With the reduction in the degree of differentiation of gastric carcinoma, the increase of invasive depth and lymph node metastasis, the positive expression rates of AnnexinⅡ, NF-κBp65, VEGF-C protein have gradually increased. It suggests that these three proteins may be correlated with the maligant degree of gastric carcinoma and the invasion and metastasis of gastric carcinoma.3. The expression of AnnexinⅡ, NF-κBp65, VEGF-C protein in gastric carcinoma was high and the relationship of them was positive correlation with each other. It suggests that these three proteins possible played synergistic effect during the process of occurrence, development, invasion and metastasis of gastric carcinoma.