Expression Of SDF-1/CXCR4 Biological Axis In Gastric Cancer And Its Clinical Significance

Gastric cancer is one of the most common malignant tumors, which has strong invasiveness, and is frequently prone to lymphatic metastasis. Also, the extent of infiltration and lymphatic metastasis has a great influence on its clinical stage and prognosis. Therefore, it is of great significance on improving the cure and survival rate of gastric cancer to study gastric cancer invasion, proliferation and metastasis [1]. The key problem is to predict tumor recurrence and metastasis and assess the prognosis of gastric cancer after comprehensive treatments including surgery, chemotherapy and radiation therapy. To solve this problem, some specific molecular markers should be used to predict the recurrence, metastasis and prognosis of gastric cancer after comprehensive treatment, which may be useful to improve the evaluation and treatment of gastric cancer further. At present, there hasn,t been a specific tumor marker to evaluate the prognosis of gastric cancer. And the study on the orientation lymphatic metastasis and recurrence of gastric cancer is few.SDF-1 / CXCR4 (chemokines) is one of the cytokine superfamily, which is a 8-12 kDa kind of secreted micromolecule polypeptide. SDF-1 / CXCR4 biologic axis play an important role in the tumor proliferation and metastasis. A recent study showed that the stromal cell-derived factor-1 (SDF-1) and CXCR4 receptor were closely related with tumor occurrence, invasion and metastasis.Tumor tissues expressed some kind of chemokine receptors and ligand specifically, while some organs expressed the corresponding chemokine ligands. So tumor cells can realize the organ-specific metastasis through the binding force between receptors and ligands. The interaction between SDF-1 and CXCR4 plays an important part in tumor invasion and organ-specific metastasis. We have studied the expression of SDF-1/CXCR4 axis and its clinical significance in gastric cancer, explored the relationship between SDF-1 / CXCR4 biologic axis and lymphatic metastasis, tumor invasion and recurrence in gastric cancer and the possible mechanisms. All these studies will provide new experimental basis for providing recurrence and prognosis of gastric cancer.Objective:To detect the protein expression of SDF-1 / CXCR4 biologic axis in gastric cancer and adjacent tissues by immunohistochemistry, to explore the relationship between expression of SDF-1 / CXCR4 biologic axis and clinical stage, lymphatic metastasis, invasion, recurrence and prognosis of gastric cancer, and to provide new theory for evaluating the prognosis of gastric cancer.Methods:(1) Immunohistochemistry was performed to detect the expression of SDF-1/CXCR4 biologic axis in gastric cancer tissues and adjacent tissues in the control group.(2) Statistical analysis was performed to investigate the relationship between SDF-1/CXCR4 expression and clinical pathological parameters of gastric cancer.(3) Logistic regression analysis was used to investigate the relationship between SDF-1/CXCR4 biologic axis and gastric cancer's clinical pathological parameters and prognosis.(4) The clinical pathological data of these cases were collected and was followed-up for 2 years.Results:(1) The expression of SDF-1/CXCR4 biologic axis in gastric carcinoma was 56.0% and 60.3%, which is significantly higher than that in the control group.(2) The expression of SDF-1/CXCR4 biologic axis was positively related with TNM stage of gastric cancer, depth of invasion, invasion to the pancreas, lymphatic metastasis (p<0.05). But it was not associated with age, sex, histopathological differentiation, tumor size and tumor site (p> 0.05).(3) The percentage of SDF-1 expression,CXCR4 expression and SDF-1/ CXCR4 coexpression in patients with lymphatic metastasis was significantly higher than that without lymphatic metastasis ( 72.4% vs 18.6%, 76.5% vs 23.2% and 70.4% vs 18.6%), (p<0.05). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of SDF-1/CXCR4 positive coexpression in gastric cancer patients with lymphatic metastasis was 74.0%, 81.4%, 89.6% and 54.7%, respectively. Logistic multivariate regression analysis showed that there was positive correlation between lymphatic metastasis and the expression of SDF-1 and CXCR4 in gastric cancer.(4) The percentage of SDF-1 expression,CXCR4 expression and SDF-1/ CXCR4 coexpression in postoperative patients with recurrence and metastasis was significantly higher than that without recurrence and metastasis. (90.6% vs 45.9%,96.9% vs 49.5% and 87.5% vs 45.0%), (p<0.05). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of SDF-1/ CXCR4 positive coexpression in postoperative gastric cancer patients with recurrence or metastasis for 2 years was 87.5%, 55.0%, 36.4% and 93.8% respectively.Conclusions:(1) SDF-1/CXCR4 was closely related with occurrence, development, the clinical stage, invasion depth and lymphatic metastasis of gastric cancer. SDF-1 / CXCR4 was expected to be the target protein for lymphatic metastasis treatment in gastric cancer.(2) The expression of SDF-1/CXCR4 was positive correlated with lymphatic metastasis, distant metastasis and recurrence of gastric cancer (P <0.05). SDF-1/CXCR4 may promote lymphatic metastasis and recurrence through accelerating the targeted movement of gastric cancer cells. (3) SDF-1/CXCR4 may be a molecular marker for lymphatic metastasis, postoperative recurrence and prognosis in gastric cancer.