The Prognostic Value Of Runx2 Expression In Breast Cancer

Objective: previous studies have shown that Runx2 is one of the most essential transcription factors for osteoblast differentiation and skeletal morphogenesis,but the role of Runx2 in metastasis in breast cancer is not very clear.Epithelial mesenchymal transition(EMT)is an important step in tumor metastasis process.The expression of Runx2 and EMT-related proteins such as Snail and E-cadherin in clinical specimens from breast cancer patients were detected by immunohistochemistry.Next we investigated the correlation between runx2 and EMT-related proteins and their prognostic value in breast cancer.Content: We performed our study from the following aspects,the nuclear expression of Runx2 and Snail protein in tumor tissues and their prognostic value of tumor patients,Runx2 overexprssion or Runx2 knock down plasmid construction,transfection and Runx2-high-expression/ Runx2-low-expression breast cancer cell culture,and the correlation between Runx2 and EMT-related proteins.Method:In this study we analyzed the Runx2 protein,Snail protein and E-cadherin from tumor tissues by immunohistochemistry and analysis was made to evaluate the relationship between the Runx2 expression and the clinicalpathological characteristics in SPSS 20.0.Survival curves were estimated using the Kaplan-Merier method and compared to the log-rank test.For multivariate analysis,Cox proportional hazard test was applied.Total RNA were extracted from breast cancer tumor cells for getting complementary DNA(c DNA)by reverse transcription.Therefore,we constructed the Runx2 eukaryon overexpression plasmid by gene cloning techniques.And then was jointed with expression vector.The recombinant plasmid was confirmed correct by DNA sequencing and transfected into breast cancer cell lines by the non-liposome transfection Fu GENE? HD Transfection Reagent.We bought the Runx2 sh-RNA plasmid and also obtained the Runx2 knock down breast cancer cell lines.Runx2 expression and EMT-related protein level were evaluated by Western blot.To the best knowledge,it is the first time to investigate the correlation of Runx2 and Snail expression and the prognostic value of their expression in breast cancer patients.Results: We have found that the high expression of Runx2 is related to the lymph node status and ER negative status and play a negative influence on prognosis,and high level of Snail expression is related to the lymph node levels and play a negative influence on prognosis.The results showed that there is a link between Runx2 and Snail expression at protein levels.In addition,the Runx2-positive/Snail-positive patients with a markedly decreased E-cadherin expression and had the worst DFS and OS.Conclusion: High level of Runx2 nuclear expression is associated the lymph nodes metastasis and was a poor prognostic marker for breast cancer patients.The correlation test showed that there may be a link between Runx2 and Snail expression in breast cancer.During the epithelial to mesenchymal transition(EMT)process of tumor cell,Runx2 protein and Snail protein may have cooperative relations to induce EMT and lead to poor survival rates.