检测乳腺癌患者血清外泌体circ PVT1与circ 0014606的表达水平，分析两者表达水平与三阴性乳腺癌（TNBC）患者临床病理及预后的关系。

回顾性分析2018年1月至2018年12月行手术治疗的84例乳腺癌患者资料，其中TNBC 46例，非三阴性乳腺癌（NTNBC）38例。另选同时期于我院进行健康体检的80例健康人群作为对照组。提取所有患者的血清外泌体，采用透射电镜和免疫印迹实验（Western blot）进行鉴定；采用qRT-PCR法分别检测TNBC、NTNBC及对照组患者外泌体中circ PVT1和circ 0014606表达水平。应用SPSS22.0分析数据，circ PVT1和circ 0014606表达水平与TNBC患者临床病理参数的关系，采用χ²或Fisher精确检验；绘制Kaplan-Meier生存曲线分析circ PVT1和circ 0014606表达与患者预后的关系。以P<0.05为差异有统计学意义。

透射电镜观察到，血清外泌体呈椭圆形双层膜囊泡结构；Western blot结果显示，外泌体特征蛋白CD9，CD63和CD81蛋白在外泌体中表达较上清液中明显升高。qRT-PCR结果显示，与对照组相比，TNBC组和NTNBC组患者血清外泌体circ PVT1和circ 0014606表达均显著上升，且TNBC患者的表达更为显著（P<0.05）。circ PVT1表达水平与TNBC患者肿瘤大小、组织学分级、TNM分期、病理类型及淋巴结转移有关（P<0.05）；circ 0014606表达水平与TNBC患者组织学分级、TNM分期、病理类型及淋巴结转移有关（P<0.05）。Kaplan-Meier分析显示，circ PVT1高表达TNBC患者3年无病生存率为46.3%，显著低于circ PVT1低表达组的71.2%（P<0.05）；circ 0014606高表达组TNBC患者3年无病生存率为40.8%，显著低于circ 0014606低表达组的68.0%（P<0.05）。

血清外泌体circ PVT1与circ 0014606在乳腺癌中高表达，TNBC中表达更为显著，且与TNBC患者临床病理及预后关系密切，有望成为判断TNBC恶性程度及预后不良的特异性指标。

Expression and clinical significance of serum exosome circ PVT1 and circ 0014606 in triple negative breast cancer

Data of 84 patients with breast cancer who underwent surgical treatment from January 2018 to December 2018 were retrospectively analyzed，including 46 patients with TNBC and 38 patients with non-triple-negative breast cancer（NTNBC）. Another 80 healthy people who underwent physical examination in our hospital during the same period were selected as the control group. The serum exosomes of all patients were extracted and identified by transmission electron microscopy and Western blot. The expression levels of circ PVT1 and circ 0014606 in exosomes of TNBC，NTNBC and control patients were detected by qRT-PCR. SPSS22.0 was used to analyze the data，and the relationship between the expression level of circ PVT1 and circ 0014606 and clinicpathological parameters of TNBC patients was analyzed by χ² or Fisher exact test. Kaplan-Meier survival curves were drawn to analyze the relationship between circ PVT1 and circ 0014606 expression and prognosis. P<0.05 was considered to be statistically significant.

Transmission electron microscopy（TEM）showed that the serum exosomes presented an elliptical bilayer vesicle structure. Western blot results showed that the expressions of exosome characteristic proteins CD9，CD63 and CD81 were significantly higher in exosome than in supernatant. qRT-PCR results showed that compared with the control group，The expression of circ PVT1 and circ 0014606 in serum exosomes in TNBC and NTNBC groups was significantly increased，and the expression was more significant in TNBC patients（P<0.05）. The expression level of circ PVT1 was correlated with tumor size，histological grade，TNM stage，pathological type and lymph node metastasis in TNBC patients（P<0.05）. The expression level of circ 0014606 was correlated with histological grade，TNM stage，pathological type and lymph node metastasis of TNBC patients（P<0.05）. Kaplan-Meier analysis showed that the 3-year disease-free survival rate of TNBC patients with high circ PVT1 expression was 46.3%，which was significantly lower than 71.2% in the group with low circ PVT1 expression（P<0.05）. The 3-year disease-free survival rate of TNBC patients in the circ 0014606 high expression group was 40.8%，significantly lower than 68.0% in the circ 0014606 low expression group（P<0.05）.

Serum exosome circ PVT1 and circ 0014606 are highly expressed in breast cancer，and are more significantly expressed in TNBC. They are closely related to the clinicopathology and prognosis of TNBC patients，and are expected to be a specific indicator for judging the malignancy of TNBC and poor prognosis.