| Gastric cancer is one of the most common malignant tumor in digestive system. The latest data show that gastric cancer worldwide incidence of cancer ranked fourth, but the mortality rate highest position of second malignancies. Our country is a big country of gastric cancer, gastric cancer mortality rate remains high, the most important reason is the existence of a significant deficiency in the early diagnosis of gastric cancer. In recent years, with advances and standardization of treatment of gastric path of global medical science gradually improve, the level of China’s treatment of gastric cancer has been greatly improved. But the status of early diagnosis and treatment of gastric cancer is still not optimistic. Most of the patients when treatment is already advanced, even if its a comprehensive treatment based on surgery, there are still 60% of patients had recurrence and metastasis, stomach cancer is currently the overall 5-year survival rate is about 30%, which seriously affecting the prognosis of patients with gastric cancer. Thus, to explore the occurrence and development mechanism of gastric cancer, stomach cancer to find new tumor markers and therapeutic targets, and further improve the early diagnosis and treatment of gastric cancer, monitoring of gastric cancer recurrence and metastasis, to carry out targeted therapy and prognosis of gastric cancer is the assessment of gastric cancer current direction and the target of basic research.SOX family genes play an important role in the diagnosis and therapy of gastric cancer. They are closely related to the occurrence and development of gastric cancer. Many researches showed that the mutation and abnormal expression of SOX family genes existed in a lot of tumors. Among the sox family genes, SOX9 gene was the one which was most extensively studied. Many studies have indicated that SOX9 is involved in the development and progression of many tumors. SOX9 was abnormally expressed in many tumors including:prostate cancer, colorectal cancer, chondrosarcoma, ovarian cancer and melanoma. SOX9 is up-regulated in many tumor cells including prostate cancer, colorectal cancer, chondrosarcoma, lung cancer, skin cancer, neurofibromatosis. However, SOX9 is also down-regulated in some tumors such as melanoma. So SOX9 may play different roles in different tumors. In this study, we detected the expression of SOX9 in gastric cancer cells, moreover, we further studied the role of SOX9 in the development and progression of gastric cancer.Carcinoembryonic antigen-related adhesion molecules 1 (CEACAM1) is a member of the carcinoembrynic antigen family (CEA). It is a transmembrane glycoprotein, which belongs to the immunoglobulin superfamily. CEACAM1 is expressed in many tissues including endothelial cells, epithelial cells, monocytes and activated T cells, B cells and natural killer cells. CEACAM1 is associated with many biological behaviors of the cells, such as cell growth, proliferation, apoptosis, migration, polarization, angiogenesis, the activation of T cells and B cells, the toxicity of T cells and natural killer cells. CEACAM1 is closely associated with the development and progression of cancers. It was reported that CEACAM1 was down-regulated in bladder cancer, liver cancer, renal cell carcinoma, breast cancer, endometrial carcinoma. Down-regulation of CEACAMl was involved in the occurrence and progression of cancers. However, in some tumors, CEACAM1 was found to be up-regulated and the up-regulation promoted the growth and metastasis of tumor cells. Thies A et al found that CEACAM1 could promote tumor growth. In another study, CEACAM1 was found to be overexpressed in lung adenocarcinoma. The expression profile of CEACAM1 in gastric cancer and its role in the metastasis and prognosis of gastric cancer was unclear. In the present study, we studied the expression of CEACAM1 in gastric canceer, and further evaluated the effect of CEACAM1 on the growth and metastasis of gastric cancer cells.Part 1 The expression of SOX9 and CEACAMl in gastric cancer tissues and its significanceObjective:To study the expression of SOX9 and CEACAM1 in normal mucosa, hyperplastic polyp, intestinal metaplasia, introepithetial neoplasia and gastric cancer, and to analyze the relationship between their expression patterns and clinical pathological parameters.Method:1. SOX9 and CEACAM1 proteins were detected by immunohistochemistry in normal mucosa, hyperplastic polyp, intestinal metaplasia, introepithetial neoplasia and gastric cancer.2. The expression of SOX9 and CEACAM1 mRNA was detected by PCR Real-time PCR in normal mucosa, hyperplastic polyp, intestinal metaplasia, introepithetial neoplasia and gastric cancer.3. Chi-square test was used to evaluate the correlation between the expression of SOX9 and CEACAM1 and the clinical pathological characteristics of the patients.Results:1. SOX9 mainly expressed bottom cells of gastric pit. The level of SOX9 protein is low in the normal gastric mucosa and hyperplastic polyps. The expression of SOX9 protein increased in intestinal epithelial metaplasia tissue. The expression of SOX9 protein further increased, in gastric epithelial neoplasia and gastric cancer tissues.2. CEACAM1 was not expressed in normal gastric mucosa and hyperplastic polyp tissues. The expression of CEACAM1 increased gradually in intestinal metaplasia tissues. The expression of CEACAM1 further increased in gastric cancer tissues. There was more CEACAM1 expressed in cytoplasm than that on the membrane in the gastric cancer.3. There was no obvious correlation between SOX9 expression and the differentiation degree of gastric cancer. The expression of SOX9 was not significantly different between intestinal and diffuse gastric cancer. However, the expression of SOX9 in N2-N3 gastric cancer tissues was significantly higher than that of NO.4. CEACAM1 expressed on the cell membrane, in the cytoplasm or simultaneously on the cell membrane and in the cytoplasm, the expression of More CEACAM1 expressed in cytoplasm in the poor differentiated gastric cancer. More CEACAM1 expressed in cytoplasm in diffuse gastric carcinoma. More CEACAM1 expressed in cytoplasm in the T3-T4 stage and N2-N3 stage gastric cancer.5. The expression of SOX9 was positively correlated with CEACAM1 in the gastric cancer tissues (r=0.124; P=0.032)6. The levels of Sox9 and CEACAM1 mRNA were low in the normal gastric mucosa and hyperplastic polyps. The expression Sox9 and CEACAM1 mRNA increased in intestinal epithelial metaplasia tissue. The expression of Sox9 and CEACAM1 mRNA further increased in gastric epithelial neoplasia and gastric cancer tissues.Conclusions:The expression of SOX9 and CEACAM1 significantly increased in gastric cancer. The expression of SOX9 was positively correlated with CEACAM1. SOX9 and CEACAM1 could promote the occurrence and development of gastric cancer.Part 2 The effect of SOX9 and CEACAM1 expression on the proliferation and metastasis of gastric cancer cellsObjective:The expression of SOX9 and CEACAM1 was knocked down by siRNA. The influence of the silence of SOX9 and CEACAM1 expression on the proliferation and metastasis of gastric cancer cell line SOX9 was evaluated.Methods:1. The expression of SOX9 or CEACAM1 was silenced by siRNA, and the effect of SOX9 or CEACAM1 knockdown on the proliferation of SGC-7901 cells was detected by MTT.2. The expression of SOX9 or CEACAM1 was silenced by siRNA, and the effect of SOX9 or CEACAM1 knockdown on the cell cycle and apoptosis of gastric cancer cells was detected by flow cytometry.3. The expression of SOX9 or CEACAM1 was silenced by siRNA, and the effect of SOX9 or CEACAM1 knockdown on the metastasis of gastric cancer cells was detected by transwell assay.Results:1. Down-regulation of SOX9 expression inhibited the growth and proliferation of gastric cancer cell line SGC-7901. But down-regulation of the CEACAM1 has no significantly effect on the growth and proliferation of gastric cancer cells.2. Down-regulation of SOX9 expression maked more cells arrest in G0-G1 phase, and induced obvious apoptosis in gastric cancer cells. Down-regulation of the CEACAM1 did not significantly affect the cell cycle distribution and cell apoptosis in gastric cancer cells.3. Down-regulation of SOX9 or CEACAM1 expression could significantly decrease the metastasis of gastric cancer cell line SGC-7901.Conclusions:Down-regulation of SOX9 could significantly inhibit the growth and invasion of gastric cancer cells, and down-regulation of CEACAM1 could inhibit the metastasis of gastric cancer cells. These results further revealed that the expression of CEACAM1 and SOX9 can promote the development of gastric cancer. SOX9 and CEACAM1 may be a new target for the treatment of gastric cancer. |
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