骨肉瘤血清外泌体整合素β4水平检测及其与临床病理特征和肺转移的相关性

Detection of serum exosomal integrinβ4 and its correlation between clinicopathological features and lung metastasis in osteosarcoma

目的:通过检测骨肉瘤患者血清外泌体整合素β4水平,分析其与临床病理特征的相关性,为骨肉瘤肺转移的预测提供理论依据。方法:收集骨肉瘤患者外周血,将患者分为术前组、术后无肺转移组及术后肺转移组,通过超高速离心法分离、提取外泌体,透射电镜对外泌体的形态及大小进行鉴定,同时应用流式细胞术鉴定外泌体特征性分子标志CD63、CD81的存在,应用流式细胞术和Western-Blot方法检测三组患者血清外泌体整合素β4水平。分析患者临床特征与血清外泌体整合素β4的相关性。结果:血清外泌体整合素β4水平:术后肺转移组>术前>术后无肺转移组,提示外泌体整合素β4与骨肉瘤肺转移相关。患者资料分析显示:外泌体整合素β4与骨肉瘤患者分期相关(P=0.01),与是否有肺转移相关(P=0.0018),与肺转移大小相关(P=0.0076),与患者性别、肿瘤部位、原发肿瘤大小、是否行术前新辅助化疗及新辅助化疗疗效无明显相关性。结论:外泌体整合素β4对骨肉瘤肺转移起到一定的预测作用,有望成为骨肉瘤肺转移的分子标志物。

Objective:To detect the level of serum exosome integrinβ4 in patients with osteosarcoma and to analyze the correlation between it and clinicopathological features,so as to provide a theoretical basis for the prediction of lung metastasis of osteosarcoma.Methods:This study included osteosarcoma who the peripheral blood of the patients was collected,and the patients were divided into the pre-operative group,the postoperative non-pulmonary metastasis group and the post-operative lung metastasis group.The morphology and size of the external urinary tract of the three groups were identified by flow cytometry and Western-Blot.Finally,the relationship between the clinical characteristics of the patient and the integrinβ4 in the serum was analyzed.Results:The results showed that the pulmonary metastasis group after operation>the preoperative group>the no pulmonary metastasis group after operation.It is suggested that exsome integrinβ4 is related to pulmonary metastasis of osteosarcoma.The analysis of patient data showed that exsome integrinβ4 was correlated with the stage of osteosarcoma patients(P=0.01).It was correlated with lung metastasis(P=0.0018),and size of lung metastasis(P=0.0076).There was no significant correlation of patient's gender,tumor location,primary tumor size,operation or not,preoperative neoadjuvant chemotherapy or not and the efficacy of neoadjuvant chemotherapy.Conclusion:Exsome integinβ4 plays a guiding role in lung metastasis of osteosarcoma.It is expected to be a molecular marker for lung metastasis of osteosarcoma.