Survival Outcomes In Breast Cancer Patients Are Associated With SDF-1/CXCR4

Background:Breast cancer was one of the major malignant diseases which threaten women’health and survival seriously in the worldwild.Distant metastasis was the main reason that caused the death of breast cancer patients. Studies have shown that chemokines and their receptors in organ-specific metastasis of breast cancer was of great significance.Muller et al have confirmed in2001, that the chemokine receptor CXCR4was highly expressed in human breast cancer cells and Its ligands CXCL12/SDF-1exhibited peak levels in common sites of metastasis in breast cancer patients such as lung,liver,lymph node and bone marrow,Numerous studies have shown that The chemokine receptor CXCR4is highly expressed in malignant breast tumors and metastases and CXCR4expression was significantly associated with poor prognosis in patients with organ-specific metastasis.Related researches suggested that,in recent year, the chemokine SDF-1also was expressed in tumor cells and which held some controversy with clinical prognosis,.A number of clinical studies of glioma, colorectal cancer,gastric cancer, and oral squamous cell carcinoma have concluded that higher SDF-1expression is correlated with lymph node and/or distant metastasis and poorer clinical outcome.Kang have created CXCL12-expressing MDA-MB-231cells by transfection of expression plasmid constructs and showed enhanced migration and invasion capacities of these cells. They also performed a gene expression analysis of human breast cancers and reported a positive correlation with recurrence and lymph node metastasis.However,some studies suggested that high SDF-1expression was Good clinical outcome indicatorsIn recent years, Kobayashiet al reported "high SDF-1expression "was a significant indicator of better clinical outcome and was related to overall survival in patients with ER-positive tumors.Valentina et al also revealed that expression of CXCL12significantly correlates with disease-free and overall Survival both in oestrogen receptor-positive and in negative breast cancers. Why the SDF-1high expression between different cancer have prognostic diversity? Whether Expression of SDF-1influence prognosis is correlated with hormone receptors and race? SDF-1of Primary tumor binded to its receptor and activated certain pathways to promote tumor cell metastasis,or SDF-1in tumor cells saturated it receptor to avoid chemotaxis towards SDF-1releasing metastasis target tissues,which need is confirm through more research.With the above-mentioned questions,the study is to detect the expression of SDF-1in primary tumor,analysis on the expression and clinicopathological characteristics and prognosis,we trying to understand mechanism of action on SDF-1and to find a new target for treatment of breast cancer.Abjective:To investigate the expression of stromal cell derived factor-1(SDF-1/CXCL12) in human breast cancer and its relationship with clinicopathologic feature and prognosis,and to looking for a new target for affecting breast cancer prognosis.Method:Paraffin wax blocks of239breast cancer patients cases were collected from Cancer Hospital of Linyi City, from2005to2008, The production of tissue microarray. immunohistochemical method was used to detect the expression and distribution Of SDF-1in tissue microarray of breast cancer.All analyzes were performed using the SPSS13.0oftware package.Comparisons between groups were evaluated using chisquared test, Fisher’s exact test,Survival curves of patients were drawn using the Kaplan-Meier method.For all the tests, differences at P<0.05were considered to be statistically significant.Result:For the entire patient cohort(Table1),"High SDF-1expression" showed a more significantly association with "High CXCR4expression", ER positive,lymph node metastasis and late aclinical stage(P<0.05), But it wasn’t correlated with Tumor size,patient age,her-2expression,nuclear grade, and distant metastasis (P>0.05)."high SDF-1expression" was detected more frequently in tumors with positive ER staining than in those with negtive ER staining (54.9%and40.2%P<0.05),and more often too in patient with positive lymph node than in those with negtive lymph node (55.8%and40.9%P<0.05).To Investigate the correlation about SDF-1expression and hormone receptors, stratified study to ER status was made and found that, in the subgroup of97 ER-negative patients(Table3),"High SDF-1expression" was positively correlated with the late clinical stage, lymph node metastasis and distant metastases (P<0.05) and was not related to patient age,Tumor size,her-2expression,nuclear grade (P>0.05).It’s puzzling to figure out that there’s no significant correlation between the expression of SDF-1and any of the clinicopathological characteristics in the122ER positive patients(Table2).we also made survival curves to analysed the correlation with SDF-1expression and disease-free survival and overall survival rates respectively among the subgroup of ER-negative and ER-positive patients, Which showed that,among the97ER negative patient, there was a significant difference in the disease-free survival and overall survival curves between the "high" and "low" expression groups(P=respectively;Fig.9,10).however,different SDF-1expression was not shown to be significantly correlated with either DFS(disease free survival) or OS(overall survival) among ER-positive patients (P>0.05,figure11,12).To seek the question about whether Expression of SDF-1influence prognosis is correlated with hormone receptors and SDF-1of Primary tumor binded to its receptor and activated certain pathways to promote tumor cell metastasis,or SDF-1in tumor cells saturated it receptor to avoid chemotaxis towards CXCL12releasing metastasis target tissues,which need is confirm through more research,We also analyse the correlation about the contemporary expression of SDF-1and CXCR4and the relation of lymph node metastasis and distant metastases,which suggested that SDF-1and CXCR4contemporary expression was significantly positively correlated with lymph node metastasis and distant metastasis in ER-negative patients, However, that had a negatively correlated trend with lymph node metastasis and distant metastasis in ER-positive patients(Table4,5).Conclusion:1:The expression of SDF-1and CXCR4was significantly correlated in breast cancer.2:High SDF-1expression was significantly correlated with lymph node involvement,distant metastasis and worse outcome in ER negative breast cancer patients.3:SDF-1expression wasn’t significantly correlated with a range of clinical and pathological features in ER-positive patients.4:There’s a significant association between CXCR4over-expression and lymph node positivity,and a tendency with distant metastasis as well, although not statistically significant. 5:SDF-1and CXCR4contemporary expression suggested a trend of positive prognosis in ER-positive patients.