Screening The Predictive Factor About Distant Metastases And Developing The Bone Metastasis Model Of Small Cell Lung Cancer

Objective:(1) To investigate the expressions of VEGF, CXCR4, TGF-β, E-cadherin, N-cadherin and MMP-9and their correlation with metastasis (major in brain and bone) and prognosis in small cell lung cancer(SCLC), and to choose the predictors in SCLC’s distant metastasis.(2) We develop a bone metastasis model of SCLC using Balb/c mouse for the next study.Methods:(1) Immunohistochemical method was used to detect the expression of VEGF, CXCR4, TGF-β, E-cadherin, N-cadherin and MMP-9in65small cell lung cancer tissues from cancer hospital of Tianjin medical university, and investigated the correlations between their expression with metastasis and prognosis of SCLC by Chi-square test and Kaplan-Meier method and COX regression.(2) Intracardiac injection of105tumor cells in the left cardiac ventricle of the Balb/c mouse to establish a bone metastasis model of SCLC.Results:(1) The E-cadherin failed to express in all the65SCLC tissues, and the other5markers were divided into two groups according to the final points, that is, the high expression group and the low expression group.①The positive expression of CXCR4and MMP-9located in cytoplasm and rates in SCLC tissues were100%(65/65) and87.7%(57/65), respectively. As to CXCR4, there were31in high expression group and34in low expression group; As to MMP-9, there were34in high expression group and31in low expression group. Significant difference of the expression rate of CXCR4was found between patients who undergoing bone metastasis or not (P=0.004), but the differences between brain metastasis or not (P=0.068) and lymph node metastasis or not (P=0.085) were not significant. High expression rate of MMP-9was significantly associated with pathology staging (P=0.048), but the difference between lymph node metastasis or not was not significant (P=0.085).②The positive expression of TGF-β and N-cadherin located in cytoplasm and rates in SCLC tissues were69.2%(45/65) and50.8%(33/65) respectively. As to TGF-β, there were28in high expression group and37in low expression group; As to N-cadherin, there were23in high expression group and42in low expression group. The expression rate of TGF-β and N-cadherin were not associated with the metastasis of SCLC.③The positive expression of VEGF also located in cytoplasm and rate in SCLC tissues was89.2%. As to VEGF, there were33in high expression group and32in low expression group. The expression rate of VEGF was not associated with the metastasis of SCLC.④nivariate analysis suggested that high expression rate of CXCR4was significantly correlated with the disease free survival (DFS) of SCLC patients (P=0.005), but high expression rate of MMP-9, TGF-β,VEGF and N-cadherin were not associated with the DFS.(P=0.341,0.183,0.275and0.225, respectively.) Multivariate analysis suggested that high expression rate of CXCR4was the independent prognostic factor for DFS in SCLC.(2)10mice were used to develop a bone metastasis model,4died of acute bleeding,3died of anesthetic complications,1was lost,1died of unknown causes in the fifteen day after puncture, and the last one had successfully suffered from bone metastasis in the left femur that was verified by CT scan and pathology.Conclusions:(1) Besides the failed expression of E-cadherin, different expression rate of VEGF, CXCR4, TGF-p, N-cadherin and MMP-9in SCLC tissues are found, and expression rate of CXCR4may be correlated with the distant metastasis of SCLC, especially in the bone metastasis. Expression rate of CXCR4is the independent prognostic factor for DFS in SCLC.(2) Intracardiac injection of tumor cells in the left cardiac ventricle of a mouse is an effective way to develop a bone metastasis model.