Role Of Aurora Kinase A And B In The Prognosis And Treatment Of Chondrosarcoma

[Background and Objective] Chondrosarcoma is the second most common malignant bone tumors following the osteosarcoma, the morbidity of Chondrosarcoma in primary malignant tumor of bone is20%. To some extent, the chondrosarcoma is not sensitive to chemotherapy and radiation therapy, due to its characteristic of increase of extracellular matrix, decrease of divided cells vessels. To date, the dominant clinical treatment for chondrosarcoma is surgical resection; however, the recurrence rate is too high (20%).At present,the molecular targeted therapy,due to its characteristic of high specificity, less injury and high efficiency, has became more and more popular. Therefore, there is an urgent need of finding a new molecular targeted therapy for chondrosarcoma.Aurora Kinase A is a member of Aurora Kinase family which has been considered as a crucial factor to regulate mitosis. It participates in the maturation and segregation Of centriole, the assembly and stabilization of spindle, the condensation of chromosome and the converging and stabilization of the median plate, etc. However, its overexpression can result in the augmentation of centriole, the formation of multiploid and the loss of p53. In various malignant tumors Aurora Kinase A had been found overexpression. Therefore, it could be considered as a prognostic factor for malignant tumors.The Aurora Kinase B is the component of the chromosome passenger protein complex which participate in the chromosome condensation, spindle assembly, segregation of sister chromatids and cytocinesis. Recent studies reported that Aurora Kinase B expressed abnormally in various malignant tumors. Furthermore, it has been showed that the activity inhibitors of Aurora Kinase could inhibit the growth of cancer cells, and some inhibitors have been applied in the pre-clinical experimental stage. Whether the Aurora Kinase A and B were expressed in the chondrosarcoma is still unknown, in this study:1.we investigated the expression of the Aurora Kinase A,B in the chondrosarcoma tissues by immunohistochemistry and analyzed its clinical significance; and we also followed-up the patients.2. We tested the effect of Aurora Kinase A,B-siRNA on cell growth of SW1353.[Materials and methods]1.72chondrosarcoma samples were randomly chosen from the Department of Pathology in Qilu Hospital of Shandong University from January2005to June2011. Meanwhile, follow-up investigation was conducted by telephone.42samples of chondroma were used as the control. Tested the expression of Aurora Kinase A and B in chondrosarcoma (72specimens)and chondroma (42specimens) by immunohistochemistry and analyze the relationship between the Aurora Kinase A,B expression and the prognosis.2. Silencing Aurora Kinase A by siRNA and tested the effect of Aurora Kinase A-siRNA on cell growth of SW1353by MTT.[Results]1. The expression of Aurora Kinase A and B in chondrosarcoma was significantly higher than that in normal cartilage tissues (p<0.01). There were differences about the expression of Aurora Kinase A and B in chondrosarcoma between the recurrence group and the non-recurrence group, metastatic group and non-metastatic group (p<0.05). The expression of Aurora Kinase A and B were significantly lower in group low grade conventional chondrosarcoma than that in groups medium and high grade conventional chondrosarcoma (p<0.01). According to the Kaplan Meier analysis and multivariate Cox regression analysis, the survival rate was significantly different between the patients with positive Aurora Kinase A and the patients with negative expression (p<0.05) and Aurora Kinase A expression was an independent risk marker of survival(HR=11.263,95%CI:2.317-54.748, P=0.003).2. MTT assay showed that the proliferation of SW1353cells two days later after RNAi was significantly lower than that of the control(P<0.05). [Conclusion] Both the Aurora Kinase A and B might involve in the oncogenic, invasive and metastatic process of chondrosarcoma; however, the mechanism is still unclear. The Aurora Kinase A could be used as a new prognostic marker and molecular therapeutic target for chondrosarcoma.