The Correlation Between The Expression Of FRAS1、 CXCL14、gp130 And Brain Metastasis With NSCLC

Background and ObjectiveLung cancer is a serious hazard to human health malignancies. Whether the world, or China, the proportion of lung cancer and death in malignant tumors rank first. Brain metastasis is one of the major causes of death. Even after active treatments, such as surgery, radiotherapy, chemotherapy, targeted therapy, Lung cancer with brain metastasis median survival is still<1 year.Tumor cells adhesion, penetration and degradation of ECM is the initial step of tumor metastasis. Therefore, ECM remodeling plays a key role in tumor metastasis. Our group used the expression profile chips to screene the gene expression differences between brain metastasis and lung cancer specimens. The result is the mRNA expression of FRAS1, CXCL14, gp130 in brain metastasis tissues waer significantly upregulated. And IHC proved FRAS1, CXCL14, gp130 protein expression in lung cancer were higher than non-lung cancer tissues.Combined with our previous have found that FRAS1, CXCL14 and gp130 mRNA were highly expressed in brain metastasis specimens; the protein expressiones were higher in lung cancer tissues than no lung cancer tissues. We guess there is correlation between the protein expression and brain metastasis. Now, we adopt immunohistochemistry to examine the expression of FRAS1、CXCL 14、gp130 in the patients with brain mastastasis and without brain metastasis to find their relationship.Methods1. Review the NSCLC patients diagnosed in comprehensive tertiary hospital in Shanghai from January 1,2008 to October 31,2013.The inclusion criteria were as follows:1) histopathologically of lung lesions confirmed NSCLC; 2) without any treatment before the diagnosis of primary tumor; 3) there was no other malignant tumor.The exclusion criteria were as follows:1) patients with NSCLC confirmed by cell pathology (lung puncture cytology, bronchoscopy brushing, etc.); 2) patients with NSCLC confirmed by metastatic sites (lymph nodes, intracranial lesions, etc.).2. NSCLC with brain metastasis determined:brain metastasis according to primary tumor diagnosis time for 3 years or less; cranial MRI suggested clear intracranial space occupying, showed significantly enhanced footprint. Following groups and exclusion criteria,30 patients were included.3. NSCLC without brain metastasis determined:according to the primary tumor diagnosis time for 3 years or more, cranial MRI suggested no intracranial space occupying. Under the control of some confounding factors, such as age, sex, smoking, stage, matching with 1:2, following groups and exclusion criteria,60 patients were included.4. Cut the patients paraffin tissue sections.5. The protein expression of FRAS1、CXCL14、gp130 were detected by immunohistochemistry.6. All statistical analyses were performed under spss 17.0 computer package. Wilcoxon test was for ordered categorical variables. Chi-square test was for unordered categorical variables. Significance was reported for a P value<0.05.Results1. In the patients with brain metastasis, the median time of brain metastasis is 5.0 months, ranging from 0 to 26 months. First brain metastasis existed in 14 cases (46.7%), while later brain metastasis existed in 16 cases (53.3%). In the 16 cases of later brain metastasis, the median time of brain metastasis is 10.73 months, ranging from 5 to 26 months. Single brain metastasis existed in 15 cases (50%), while multiple brain metastases existed in 12 cases (40%), unkonw in 3 cases (10%). Brain metastasis limited to brain existed in 14 cases (46.7%), while brain metastasis not limited to brain existed in 12 cases (40%), unknow is 4 cases (13.3%).2. There are no statistically significant differences in histological type and degree of differentiation between brain metastasis and no brain metastasis (P values respectively is 0.965、0.100)3. There is statistically significant difference in FRAS1 protein expression between brain metastasis and no brain metastasis (P=0.002)4. There are no statistically significant differences in CXCL14 and gp130 protein expression between brain metastasis and no brain metastasis (P values respectively is 0.746、0.888) Conclusion1. In lung tissue of NSCLC, the poorly differentiation may be associated with barain metastasis.2. In lung tissue of NSCLC, FRAS1 protein overexpression may be associated with brain metastasis.3. In lung tissue of NSCLC, CXCL14 and gp130 protein expression have nothing with brain metastasis.